Influence of Ethanol as a Co-Solvent in Cyclodextrin Inclusion Complexation: A Molecular Dynamics Study

Molecular dynamics (MD) simulations were used to investigate the dynamics and host-guest interactions of the inclusion complexes between a potent anti-HIV agent, UC781, and three different types of cyclodextrins (CDs) including βCD, 2,6-dimethyl-βCD (MβCD), and 2-hydroxypropyl-βCD (HPβCD) in aqueous solution with ethanol (EtOH) as a co-solvent. The MD simulation results revealed that EtOH as the co-solvent and the type of cyclodextrin affected the inclusion complex formation. From this study, UC781/MβCD provided the most stable inclusion complex. The competition for the cavity of βCD between UC781 and EtOH and the ensuing occupation of βCD cavities by EtOH resulted in a weaker interaction between βCD and UC781. In HPβCD, a supramolecular complex of UC781−HPβCD−EtOH was formed. The EtOH could easily fill the residual void space of the interior of unoccupied HPβCD due to the movement of UC781. In MβCD, the strong hydrogen bond interactions between the UC781 amide group and the secondary hydroxyl groups of MβCD significantly stabilized the inclusion complex in the presence of EtOH.     

联合应用激光微切和实时定量RT-PCR检测单个胰岛的基因表达

在显微镜下用紫外激光微切机将单个胰岛从胰腺切片中切下，提取RNA后逆转录成cDNA并在实时定量RY—PCR中得到有效的扩增，其表达量与细胞数量成正比。     

Ten years' experience in aortic valve replacement with homografts in 389 cases

BACKGROUND AND AIM OF THE STUDY: Aortic valve replacement using homografts is an accepted alternative to the use of other replacement devices, and has been established at the authors' institution for more than 10 years. METHODS: Since 1992, a total of 389 homografts was implanted, and 332 patients (mean age 54 years, 72% males) were followed up. The initial patients (n = 75) had subcoronary implantation, all subsequent patients had root replacement. Both aortic grafts (AG) and pulmonary grafts (PG) were used. Follow up was conducted with regard to the factors 'graft origin', 'implantation technique' and 'gender', and included clinical examination, ECG and transthoracic echocardiography on an annual basis. RESULTS: Overall 30-day mortality was 5.4% (AG patients 3.9%, PG patients 13.5%; p = 0.09). Among late deaths (n = 22), six were valve-related (all prosthetic infection). Four minor thrombembolic events were recorded due to amaurosis fugax and transient ischemic attacks (TIA). Freedom from reoperation was 86.5%. Indication for graft replacement was greater after subcoronary implantation than after root implantation (p = 0.04). Reoperation was necessary in 24 patients due to restenosis (n = 4), regurgitation grade >II (n = 5), paravalvular leak (n = 2) and prosthetic infection (n = 13). At the latest echocardiographic follow up, mean peak pressure gradient was 15.60 +/- 11.76 mmHg, homograft regurgitation grade was 0.82 +/- 0.66, left ventricular end-diastolic diameter (EDD) was 49.1 +/- 7.54 mm, and mean aortic root diameter was 30.54 +/- 5.48 mm. When comparing parameters at a mean of five years postoperatively, the pressure gradient increased from 10.26 to 15.02 mmHg, regurgitation grade increased from 0.53 to 0.81, and EDD decreased from 52.3 to 50.4 mm. Other variables showed no significant differences. CONCLUSION: The present results confirmed good midterm-results for aortic valve replacement with homografts. These prostheses are vulnerable to infection, and root replacement was superior to the subcoronary implantation technique.     

Impact of ramipril versus other angiotensin-converting enzyme inhibitors on outcome of unselected patients with ST-elevation acute myocardial infarction

We examined the impact of treatment with ramipril versus other angiotensin-converting enzyme (ACE) inhibitors on clinical outcome in unselected patients of the prospective multicenter registry Maximal Individual Therapy of Acute Myocardial Infarction PLUS registry (MITRA PLUS). Of 14,608 consecutive patients with ST-elevation acute myocardial infarction, 4.7% received acute therapy with ramipril, 39.0% received other ACE inhibitor therapy, and 56.3% received no ACE inhibitor therapy. In a multivariate analysis, the treatment with ramipril compared with the treatment without ACE inhibitors was associated with a significantly lower hospital mortality and a lower rate of nonfatal major adverse coronary and cerebrovascular events. Compared with other generic ACE inhibitors, ramipril therapy was independently associated with a significantly lower hospital mortality (odds ratio [OR] 0.54, 95% confidence interval [CI] 0.32 to 0.90) and a lower rate of nonfatal major adverse coronary and cerebrovascular events (OR 0.65, 95% CI 0.46 to 0.93), but not with a lower rate of heart failure at discharge (OR 0.79, 95% CI 0.50 to 1.27).     

Patients with Persistent Atrial Fibrillation Taking Oral Verapamil Exhibit a Lower Atrial Frequency on the ECG

Background: While there is agreement that verapamil attenuates the AF‐ induced refractory period shortening when given before AF induction, controversy exists regarding its effects when given after the onset of persistent AF. This study aimed to compare atrial fibrillatory frequency obtained from the surface ECG in patients with persistent atrial fibrillation (AF) with oral verapamil treatment to those without this treatment. Methods and Results: Surface ECG recordings were performed in 57 patients (34 male, 23 female, mean age 59 ± 11 years) with persistent AF (> 7 days). The frequency content of the fibrillatory baseline was quantified using digital signal processing (filtering, QRST complex averaging and subtraction. Fourier transformation). In 27 patients with verapamil treatment (120 or 240 mg/day for at least 7 days) mean fibrillatory frequency measured 6.4 ± 0.2 Hz, compared to 7.0 ± 0.4 Hz (P = 0.012) in 30 patients without verapamil. In a subset of 20 randomly selected patients (10 with, 10 without verapamil treatment) a 24‐hour Holter ECG recording was performed and fibrillatory frequency determined at 4 PM, 10 PM, 4 AM, and 10 AM. While there was a significant frequency reduction in the verapamil treated patients at night (P = 0.011), it remained constant over time in the other patients. Conclusion: In patients with persistent AF, fibrillatory frequency assessed by spectral analysis of the surface ECG is lower in patients taking verapamil. A.N.E. 2002;7(2):92–97     

Efficacy of extended-release niacin with lovastatin for hypercholesterolemia: assessing all reasonable doses with innovative surface graph analysis

BACKGROUND: Combination therapy to improve the total lipid profile may achieve greater coronary risk reductions than lowering low-density lipoprotein cholesterol (LDL-C) alone. A new extended-release niacin (niacin ER)/lovastatin tablet substantially lowers LDL-C, triglyceride, and lipoprotein(a) levels and raises high-density lipoprotein cholesterol (HDL-C) level. We evaluated these serum lipid responses to niacin ER/lovastatin at all clinically reasonable doses. METHODS: Men (n = 85) and women (n = 79) with type IIa or IIb primary hyperlipidemia after diet were randomized among 5 parallel treatment arms. Each arm had 5 sequential 4-week treatment periods: niacin ER (starting at 500 mg/d, increasing in 500-mg increments to 2500 mg/d); lovastatin (starting at 10 mg, increasing to 20 mg, then 40 mg/d); and 3 combinations arms, each with a constant lovastatin dose and escalating niacin ER doses. RESULTS: For primary comparisons, mean LDL-C level reductions from baseline were greater with niacin ER/lovastatin (1500/20 mg) than with lovastatin (20 mg) (35% vs 22%, P<.001) and with niacin ER/lovastatin (2000/40 mg) than with lovastatin (40 mg) (46% vs 24%, P<.001). Each 500-mg increase in niacin ER, on average, decreased LDL-C levels an additional 4% and increased HDL-C levels 8%. The maximum recommended dose (2000/40 mg/d) increased HDL-C levels 29% and decreased LDL-C levels 46%, triglyceride levels 38%, and lipoprotein(a) levels 14%. All lipid responses were dose dependent and generally additive. Graphs of the dose-response relationships as 3-dimensional surfaces documented the strength and consistency of these responses. CONCLUSIONS: Niacin ER/lovastatin combination therapy substantially improves 4 major lipoprotein levels associated with atherosclerotic disease. Dose-response surfaces provide a practical guide for dose selection.     

Time dependence of defibrillator benefit after coronary revascularization in the Multicenter Automatic Defibrillator Implantation Trial (MADIT)-II.

OBJECTIVES: The study was designed to assess the effect of elapsed time from coronary revascularization (CR) on the benefit of the implantable cardioverter-defibrillator (ICD) and the risk of sudden cardiac death (SCD) in patients with ischemic left ventricular dysfunction. BACKGROUND: The ICD improves survival in appropriately selected high-risk cardiac patients by 30% to 54%. However, in the Coronary Artery Bypass Graft (CABG)-Patch trial no evidence of improved survival was shown among a similar population of patients in whom an ICD was implanted prophylactically at the time of elective CABG. METHODS: The outcome by time from CR was analyzed in 951 patients in whom a revascularization procedure was performed before enrollment in the Multicenter Automatic Defibrillator Implantation Trial (MADIT)-II. RESULTS: The adjusted hazard ratio (HR) of ICD versus conventional therapy was 0.64 (p = 0.01) among patients enrolled more than six months after CR, whereas no survival benefit with ICD therapy was shown among patients enrolled six months or earlier after CR (HR = 1.19; p = 0.76). In the conventional therapy group, the risk of cardiac death increased significantly with increasing time from CR (p for trend = 0.009), corresponding mainly to a six-fold increase in the risk of SCD among patients enrolled more than six months after CR. CONCLUSIONS: In patients with ischemic left ventricular dysfunction, the efficacy of ICD therapy after CR is time dependent, with a significant life-saving benefit in patients receiving device implantation more than six months after CR. The lack of ICD benefit when implanted early after CR may be related to a relatively low risk of SCD during this time period.     

Inflammatory, abscess-forming foreign body reaction mimics a thrombus formation on an atrial septal defect closure device: A commented case report.

We are presenting a case of floating left and right atrial formations on an atrial septal defect occluder system (23mm StarFLEX)-Occluder) initially supposed to be thrombotic appositions in a 57-year-old man. The closure was performed on the background of left hemispheric stroke and atrial septal aneurysm (ASA) with patent foramen ovale (PFO). The suspect structures were detected in the 6-month follow-up by transesophageal echocardiography (TEE). The patient underwent a successful surgical explantation of the closure device and closure of the patent foramen ovale (PFO) using a pericardial patch. The pathological evaluation of the biatrial device associated appositions revealed hytrophic heart muscle tissue with perifocal scarring and purulent abscess-forming, granulating and foam-cell including inflammatory foreign body reaction instead of the expected thrombus formation.