扩张型心肌病患者外周血单个核细胞NF-κB/p65的表达及阿托伐他汀钙的影响

目的探讨扩张型心肌病（DCM）患者外周血单个核细胞（PBMCs）核转录因子xappaB（NF—κB）／p65的表达及阿托伐他汀钙（Ale）的干预作用。方法对25例DCM患者和18名健康对照者分离出的PBMCs进行培养，共培养24h，并将培养的PBMCs分成3组：空白对照组、脂多糖（LPS）组和Ale组。对3组培养后的PBMCsNF—κB／p65的表达进行免疫组化染色检测和半定量分析。结果DCM患者PBMCsNF—κB／p65胞核染色阳性率明显高于健康对照者[（14．86±3．21）％比（6．32±2．25）％，P〈0.01]；脂多糖组DCM患者和健康对照者PBMCsNF—κB／p65胞核染色阳性率与空白对照组比较均显著增加（P〈O．01）；Ale组DCM患者和健康对照者PBMCsNF—κB／p65胞核染色阳性率与脂多糖组比较则显著下降（P〈0．01）。结论DCM患者NF—κB／p65表达增高，而Ale可下调脂多糖刺激下NF-κB／p65表达增高。     

Current approaches in the treatment of Alzheimer's disease.

The management of Alzheimer's disease (AD) has been a long-standing challenge and area of interest. Advances in knowledge of the pathogenesis of disease and an increase in disease burden have prompted investigation into innovative therapeutics over the last two decades. This article reviews the various treatments of AD including those targeted towards cholinergic deficiency, oxidative stress, the amyloid cascade, inflammation, and excitotoxicity. Second generation cholinesterase inhibitors remain the preferred therapy for early and intermediate AD while the glutamate antagonist, memantine, is also approved for advanced stages of disease. Antioxidants may delay disease progression, while data on other experimental therapies remain equivocal at best. Gene therapy directed at neurotropins is currently under investigation with some intriguing preliminary results; however, the number of patients examined is too few to be conclusive. Drugs directly targeting amyloid-beta, particularly the amyloid-beta vaccine, continue to be investigated and their forthcoming results are eagerly anticipated.     

Spontaneous compartment syndrome in a patient with diabetes and statin administration: a case report

Compartment syndrome is a condition characterized by pressure increasing in the inextensible muscular compartments that leads to a decrease of capillary perfusion with consequent ischemic lesions of the logia elements. The authors report a case of an unusual compartment syndrome with spontaneous onset in a patient with type II diabetes and chronic therapy with statins (Atorvastatin). The condition was successfully treated by a fasciotomy and medical support. The importance of a correct anamnesis and a high level of suspicion is emphasized.     

他汀类药物联合抗血小板药物降低冠状动脉搭桥术后血管再狭窄的研究

冠状动脉旁路移植术（CABG）是治疗冠心病有效手段之一,但是其术后易发生桥静脉再狭窄甚至闭塞,发生复发性心绞痛、心肌梗死以及再次血运重建的风险增加。抗血小板药物和他汀类药物是临床提高桥血管通畅率的常用药物,抗血小板药物能减少早期的血栓形成,他汀类药物能够延缓中期的内膜增厚和晚期的粥样斑块的形成。本文就联合使用抗血小板药物和他汀类药物降低CABG术后血管再狭窄的研究作一综述,并对综合治疗CABG术后血管再狭窄的方法进行展望。     

Dose-dependency in pleiotropic effects of atorvastatin

Statins are recognized as the principal and most effective class of drugs for reducing serum cholesterol levels and, therefore, significantly reducing cardiovascular events and mortality. Statins may have a wide range of beneficial biological effects in addition to lipid lowering, a phenomenon commonly termed a 'pleiotropic effect'. However, the dose-dependency of these effects remains unclear. The present study evaluated whether atorvastatin, a potent statin, ameliorates the serum markers of pleiotropic effects, with a focus on dose-dependency. The pleiotropic effects of treatment with atorvastatin 5 mg/day and 10 mg/day for six months each in 15 patients with primary hypercholesterolemia were assessed in a prospective, randomized, open-label, crossover, single-centre study. Atorvastatin treatment dose-dependently decreased a serum marker of oxidative stress as well as the serum low-density lipoprotein cholesterol level. However, serum markers of inflammation and fibrinolysis decreased independently of dose. In conclusion, the dose-dependency of atorvastatin's pleiotropic effects differs among individual biological effects.     

Effect of pravastatin, simvastatin and atorvastatin on the phagocytic activity of mouse peritoneal macrophages

Since cholesterol and lipid content may affect cell membrane fluidity, we assumed that treatment of mice with lipid lowering statins would enhance the engulfing capacity of their macrophages. Four groups of animals were examined. Group I-treated with pravastatin, group II--with simvastatin--both drugs in a dosage of 40 mg/kg daily, 5 days/week for a total of 3 weeks. Mice in group III received atorvastatin 5 mg/kg for the same time period. Group IV--untreated animals serving as controls. The phagocytic capacity of the peritoneal macrophages was evaluated by their ability to engulf latex particles. In addition, the mitogen response of the peripheral blood mononuclear cells (PBMC) and splenocytes to Con A and PHA was examined. Compared to the controls, the percentage of phagocyting cells in pravastatin-treated mice was enhanced by 18%, with simvastatin--by 24% and in atorvastatin-treated animals by 8%. The three statins increased the phagocytic index by 79.5%, 88.8% and 62%, respectively. The mitogen response of splenocytes from mice treated with the three statins to Con A increased by 68%, 48% and by 40%, respectively. Compared with the controls the response to PHA was higher in animals treated with pravastatin (84%), simvastatin (73%) and atorvastatin (57%). The response of PBMC from statin-treated animals to both mitogens did not differ from that of the controls. The results suggest that statins, at least those hereby investigated, may exert a beneficial effect on the immune function of the macrophages.     

Cholesterol and Alzheimer's disease--is there a relation?

The predominating theory on the pathophysiology of Alzheimer's disease (AD) concerns the mis-metabolism of amyloid precursor protein (APP). As a result of this mis-metabolism, there is an increased production of the 42 amino acid form of beta-amyloid (Abeta42) that rapidly will form oligomers that initiates a cascade of events leading to the accumulation of amyloid plaques. Commonly recognised as vascular factors, hypertension, hypercholesterolemia and diabetes and the inheritance of the epsilon4 allele of the APOE gene, are also risk factors for AD. These risks have been found to promote the production of Abeta42. An association between cholesterol and the development of AD was suggested in the early 1990s and ever since, an increasing amount of research has confirmed that there is a link between cholesterol and the development of AD. A high cholesterol levels in mid-life is a risk for AD and statins, i.e., cholesterol-lowering drugs, reduce this risk. Statins may not only inhibit enzymes involved in the endogenous synthesis of cholesterol but also affect enzymes involved in Abeta metabolism, i.e., alpha-secretase and beta-secretase. This normalises the breakdown of APP thereby promoting the non-amyloidogenic pathway. In this review, investigations focusing on cholesterol and Alzheimer's disease are presented.     

Ezetimibe-associated myopathy in monotherapy and in combination with a 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitor

Two cases of myopathy associated with ezetimibe are reported. In the first case, a woman on ezetimibe monotherapy presented with muscle pain and an elevated concentration of creatine kinase (CK) on two occasions, with ezetimibe 10 mg and with ezetimibe 5 mg after a washout period. The recurrence of muscle pain after washout and the CK increase both supported the hypothesis that ezetimibe alone can be linked to myalgia. In the second case, a man had been treated with atorvastatin, and ezetimibe 10 mg was added to improve his lipid profile. Two months later, the patient complained of muscle pain and a CK increase was noted. The appearance of symptoms when adding ezetimibe to atorvastatin supports a potential pharmacokinetic and/or a pharmacodynamic interaction between these two drugs. These cases suggest that ezetimibe monotherapy as well as ezetimibe associated with the use of a statin may induce myalgia. The mechanism by which ezetimibe could cause muscle pain is not known.