Pathophysiology and treatment of atherosclerosis

Recent years have brought a significant amount of new results in the field of atherosclerosis. A better understanding of the role of different lipoprotein particles in the formation of atherosclerotic plaques is now possible. Recent cardiovascular clinical trials have also shed more light upon the efficacy and safety of novel compounds targeting the main pathways of atherosclerosis and its cardiovascular complications.In this review, we first provide a background consisting of the current understanding of the pathophysiology and treatment of atherosclerotic disease, followed by our future perspectives on several novel classes of drugs that target atherosclerosis. The focus of this update is on the pathophysiology and medical interventions of low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), triglycerides (TG) and lipoprotein(a) (Lp(a)).     

Antibiotic treatment of ulcerative enteritis of bobwhite quail

Penicillin-streptomycin, bacitracin methylene disalicylate, zinc bacitracinm, soluble bacitracin methylene disalicylate, streptomycin (25%) and spectinomycin were used as prophylactic and therapeutic treatments for ulcerative enteritis in bobwhite quail (Colinus virginianus). Penicillin-streptomycin was the most effective prophylactic and streptomycin (25%) was the most effective therapeutic agent.     

Recent developments in the treatment of atherosclerosis

Atherosclerosis is one of the most frequent causes of cardiac arrest. The major cause of this disease is high concentrations of lipid in the blood. Medicinal agents so far have been quite successful in the management of hyperlipidemia. Among the several widely used drugs, (fibrates, statins and niacin) statins are the most frequently prescribed in many forms of hyperlipidemia. Recently, statins have been found to produce serious toxicities, which are rare but can be potentially harmful and are noise concern for the immediate need to develop some new chemical entities in this category. This review is primarily concerned with recent developments in atherosclerotic drug discovery including novel inhibitors of cholesterol biosynthesis, cholesterol absorption inhibitors and antioxidants. The review also focuses on possible future targets including gene therapy.     

Antibiotic treatment of abscesses of the central nervous system.

Samples of intracranial pus and serum from 32 patients were assayed to determine the concentrations reached in them of penicillin, ampicillin, cloxacillin, cephaloridine, gentamicin, chloramphenicol, fusidic acid, and lincomycin. Metronidazole had not been given. Penicillin penetrated abscesses reasonably well, but other beta-lactam antibiotics did not. The penetration of chloramphenicol was erratic. Aminoglycosides penetrated poorly, but lincomycin and fusidic acid penetrated well. Assay of sulphonamides and co-trimoxazole in pus was unreliable. These studies indicate that treatment of abscesses of the central nervous system should be considered according to the site and the likely antecedent cause. Abscesses of sinusitic origin, usually in the frontal lobe, yield penicillin-sensitive streptococci. Penicillin is the drug of choice. Abscesses of otitic origin, usually in the temporal lobe, yield a mixed flora, often including anaerobic bacteria. Multiple antibiotic therapy is indicated. Abscesses of metastatic or cryptogenic origin yield streptococci or mixed cultures, and multiple therapy is appropriate while awaiting the bacteriological results. Spinal and post-traumatic abscesses yield Staphylococcus aureus, and fusidic acid is the drug of choice.     

Antibiotic treatment and post-handling survival of reindeer calves in Alaska

Free ranging reindeer (Rangifer tarandus tarandus) are driven into corral systems and handled each summer on the Seward Peninsula (Alaska, USA). During June and July of 1995-96 reindeer calves were inspected for injury, handled, weighed, and randomly treated with long-acting oxytetracycline. Calves that returned to subsequent handlings within the same year, received treatment only if they had been treated during their first handling. The effects of prophylactic antibiotic treatment and other factors, including weight, handling related injury, and sex on post-handling survival in reindeer calves were evaluated. Return rates of yearlings in 1996 and 1997 were analyzed using logistic regression. Weight change of calves between handlings was examined using a general linear model. Calf weight and handling injury were the only factors that significantly affected calf survival. No factor had a significant effect on calf weight change between handlings. Apparently, long-acting oxytetracycline was not an effective prophylactic treatment for this capture operation. The benefits of prophylactic antibiotic treatment have not been quantified and further studies of the effects and efficacy of prophylactic treatments are recommended. Ineffective treatments should be avoided because they may add additional stress to the captured animal. Managers should evaluate the potential effectiveness of a prophylactic treatment before indiscriminately applying one. Preventing calf injuries was the most effective method of reducing post-handling mortality in this study and should be given a high priority in the design of capture operations.     

间充质干细胞在动脉粥样硬化治疗中的研究进展

动脉粥样硬化是一种病因复杂的血管壁慢性炎症性疾病。动脉粥样硬化及其相关并发症已成为人类死亡的主要原因,然而,其病因和发病机制尚未完全阐明,治疗效果还不满意。目前已经证实,动脉内皮细胞功能发生障碍是动脉粥样硬化的始动过程,内皮细胞功能失调和内皮细胞丢失是动脉粥样硬化症的主要特点;而血管平滑肌细胞的异常增生在动脉粥样硬化的发生发展中也扮演着重要角色。因此,探索有效措施促进有益的内皮细胞再生并抑制平滑肌细胞增生是血管损伤防治的关键。近年来有研究发现,体外输注的间充质干细胞能够向受损部位募集,并进一步分化为内皮细胞,修复损伤血管。然而,也有研究显示体外输注的间充质干细胞还可以分化为血管平滑肌细胞进而在血管局部增生,参与血管再狭窄的发生。文中综述了间充质干细胞输注对动脉粥样硬化发展的最新研究进展,希望为后续开展的用间充质干细胞治疗动脉粥样硬化的研究提供一定的参考。     

Pharmacological basis of different targets for the treatment of atherosclerosis

The development of atherosclerotic plaque is a highly regulated and complex process which occurs as a result of structural and functional alterations in endothelial cells, smooth muscle cells (SMCs), monocytes/macrophages, T-lymphocytes and platelets. The plaque formation in the coronary arteries or rupture of the plaque in the peripheral vasculature in latter stages of atherosclerosis triggers the onset of acute ischemic events involving myocardium. Although lipid lowering with statins has been established as an important therapy for the treatment of atherosclerosis, partially beneficial effects of statins beyond decreasing lipid levels has shifted the focus to develop newer drugs that can affect directly the process of atherosclerosis. Blockade of renin angiotensin system, augmentation of nitric oxide availability, reduction of Ca(2+) influx, prevention of oxidative stress as well as attenuation of inflammation, platelet activation and SMC proliferation have been recognized as targets for drug treatment to control the development, progression and management of atherosclerosis. A major challenge for future drug development is to formulate a combination therapy affecting different targets to improve the treatment of atherosclerosis.     

Proteomic profiling during atherosclerosis progression: Effect of nebivolol treatment

There is a great need for the identification of biomarkers for the early diagnosis of atherosclerosis and the agents to prevent its progression. The aim of this study was to explore the effect of 24 week of nebivolol (a third-generation vasodilatory beta-blocker) treatment on serum protein profiles in Apo E^?/? mice during atherosclerosis progression. Nebivolol treated and non-treated (the control group) groups consisted of 10 genetically modified homozygous Apo E^?/? mice. Proteomic analyses were performed using surface-enhanced laser desorption/ionization time-of-flight mass spectrometry (SELDI-TOF MS) in the serum samples from the nebivolol treated and non-treated Apo E^?/? mice. The protein profiles obtained using three different chips, CM10 (weak cation-exchange), H50 (reverse phase), and IMAC30-Cu²⁺ (immobilized metal affinity capture) were statistically analyzed using the ProteinChip data manager 3.0 program. At the end of 24 week of nebivolol-treatment period, a total of 662 protein/peptide clustering peaks were detected using 12 different conditions and reading with high and low intensity laser energy. The highest total number of protein/peptide clusters was found on H50 chip array. The peak intensities of 95 of the 662 protein/peptide clusters were significantly different in the nebivolol-treated atherosclerotic group in comparison to the non-treated control mice groups (P < 0.05). Forty-three protein/peptides were up-regulated (high signal intensity) while 52 protein/peptides had lower signal intensity (down-regulated) in the nebivolol-treated atherosclerotic group. The proteomic profiles of nebivolol-treated Apo E^?/? mice were different than the control group indicating a potential role of nebivolol in atherosclerosis. Our study contributes to understand the efficacy of nebivolol on serum protein/peptide profiles during atherosclerosis development.     

含铜抗菌不锈钢的抗菌性能研究

对铁素体和奥氏体2种含铜抗菌不锈钢的抗菌性能进行了考察.采用覆膜法检测抗菌率,用透射电镜观察与铁素体抗菌不锈钢作用后的大肠埃希菌细胞形态.2种抗菌不锈钢材料对供试的 17 株常见菌,除产气肠杆菌外均显示较强的抗菌性能,抗菌谱广;铁素体和奥氏体对1×107 cfu/mL及以下浓度的大肠埃希菌在 24 h内杀灭率达到99%;铁素体和奥氏体分别在作用 3 h和 9 h时可将1×107 cfu/mL的大肠埃希菌全部杀灭;打磨次数和环境温度的变化不影响2种抗菌不锈钢的杀菌率;透射电镜结果显示,与抗菌不锈钢作用后的大肠埃希菌菌体结构松散,细胞壁和细胞膜破裂,有内容物漏出.铁素体和奥氏体抗菌不锈钢均具优良的抗菌性能,抗菌谱广,与其作用后的细菌菌体破裂,有内容物溶出,最终致菌死亡.