水飞蓟宾—卵磷脂复合物红外光谱和磁核磁共振波谱特征

目的：研究水飞蓟滨－卵磷脂复合物（SLC）中水飞蓟宾与卵磷脂之间是以共价键还是以其他次级键结合。方法；应用红外光谱、磷核磁共振波谱方法对本室合成的水飞蓟宾－卵磷脂复合物进行检测分析。结果：水飞蓟宾－卵脂复合物具有水飞蓟宾和卵磷脂的红外光谱特征，其磷核磁共振波谱显示水飞蓟宾和卵磷脂间以非共价键结合。结论：水飞蓟宾－卵磷脂是以非共价键结合，未形成新的化合物，二者自身化学性质在体内不会改变。     

水飞蓟宾-卵磷脂复合物对水飞蓟素胶囊的相对生物利用度研究

目的:评价水飞蓟宾-卵磷脂复合物对水飞蓟素胶囊的相对生物利用度。方法:选择22例20～40岁健康成年男性受试者,随机分为两组,自身前后交叉依次口服水飞蓟宾-卵磷脂复合物胶囊8粒(相当于水飞蓟宾280mg)和水飞蓟素胶囊2粒(相当于水飞蓟素280 mg,含水飞蓟宾112 mg),应用高效液相色谱法测定各受试者给药后不同时间点的血药浓度,并用3P97软件计算药动学参数。结果:水飞蓟宾-卵磷脂复合物和水飞蓟素胶囊的实测T_(max)分别为(1．53±0．68)和(1．51±0．84)h;实测C_(max)分别为(3525．2±1852．1)和(412．0±241．1) ng·mL~(-1);梯形法计算AUC_(0～11h)分别为(5064．1±1881．6)和(842．0±327．3)ng·h·mL~(-1);t_(1/2)β分别为(2．41±0．61)和(2．30±0．62)h。经统计学分析,两者的AUC_(0～11h)和C_(max)有显著性差异(P＜0．05)。水飞蓟宾-卵磷脂复合物对于水飞蓟素胶囊的相对生物利用度为(270．4±139．6)%。结论:水飞蓟宾-卵磷脂复合物的生物利用度优于水飞蓟素胶囊。     

水飞蓟宾-卵磷脂复合物制备工艺比较

目的建立实验室制备水飞蓟宾 卵磷脂复合物的方法。方法将水飞蓟宾和卵磷脂共溶于不同溶剂中 ,在一定条件下进行反应 ,然后将反应物分离、干燥、称重 ,比较收率。结果水飞蓟宾和卵磷脂可共溶于乙醇和热丙酮中。二者在 5 5℃乙醇中反应不完全 ,收率很低 (2 7% ) ,制备物为红棕色 ,不易干燥。二者在 5 5℃热丙酮中反应 10min和 70min ,收率分别为 5 9%和 93% ,制备物为黄白色类结晶固体物 ,易于干燥。结论此制备工艺中影响收率和质量的主要因素是反应介质的性质与反应时间     

水飞蓟宾磷脂复合物的制备与大鼠生物利用度的研究

目的制备水飞蓟宾磷脂复合物并对其理化性质进行考察，比较水飞蓟宾磷脂复合物与水飞蓟宾原料在大鼠体内的生物利用度。方法以丙酮为溶剂，加入水飞蓟宾和大豆磷脂，充分搅拌至澄清，真空干燥即得黄白色固体；用DSC，UV，IR等方法测定水飞蓟宾磷脂复合物的理化性质；两组大鼠分别灌胃给予水飞蓟宾磷脂复合物和水飞蓟宾原料后，用RP-HPLC法测定不同时间血浆中总的和游离的水飞蓟宾的浓度，通过3P97程序计算药代动力学参数。结果研究表明水飞蓟宾磷脂复合物是以非共价键结合，而不是新的化合物；水飞蓟宾磷脂复合物明显改善了水飞蓟宾在水中及正辛醇中的溶解性能；大鼠灌胃给予水飞蓟宾磷脂复合物，体内吸收符合一级吸收一室模型，血浆中游离药物和总的药物浓度的T_max分别为10 min和2 h；C_max分别为0.11和1.08 μg·mL^-1；T_1/2分别为2.18和3.84 h；AUC_0～∞分别为1.71和12.94 μg·mL^-1·h，而给予水飞蓟宾原料，大鼠体内吸收的浓度在检测限以下，不能测定。结论水飞蓟宾磷脂复合物与水飞蓟宾原料相比亲脂性显著增加，从而增强了水飞蓟宾在胃肠道中的吸收，提高了水飞蓟宾的口服生物利用度。     

胶束电动毛细管色谱法测定水飞蓟素及其制剂中主要有效成分含量

目的　建立一种胶束电动毛细管色谱分离测定水飞蓟素及其制剂Legalon胶囊、益肝灵片中水飞蓟宾、异水飞蓟宾、水飞蓟亭、水飞蓟宁含量的方法。方法　选用缓冲液为30 mmol.L^-1硼砂-50 mmol.L^-1去氧牛磺胆酸-20 mmol.L^-1 β-环糊精,pH为9.2,运行电压20 kV,压差进样,进样时间3 s,检测波长为288 nm,温度为室温。内标为芦丁。结果　样品中各组分的平均回收率分别为水飞蓟亭99.9％,水飞蓟宁98.3％,水飞蓟宾99.0％,异水飞蓟宾98.2％。结论　此法准确、灵敏,且能分离水飞蓟宾、异水飞蓟宾的非对映异构体。     

水飞蓟宾-磷脂复合物的药代动力学和药效学研究进展

结合一系列体外实验、动物实验、人体实验及临床试验，综述水飞蓟宾-磷脂复合物的药代动力学、药效学及其安全性与耐受性的研究进展。大量的研究表明，与普通水飞蓟宾制剂相比，水飞蓟宾-磷脂复合物脂溶性增大，更容易透过细胞膜，吸收加快，生物利用度提高，活性增强，极具临床应用和研究价值。     

水飞蓟素抗肝损伤及治疗糖尿病并发症作用的研究

主要综述近3年水飞蓟素、水飞蓟宾和水飞蓟宾-磷脂复合物在药理和临床上新的应用.这些化合物具有抗氧化、抗脂质过氧化、抗纤维化、抗炎症、细胞膜稳定、免疫调节和肝再生等活性.它们最常用作肝保护剂,也应用于拮抗糖化氧化和胰岛素增敏活性以及抗糖尿病、治疗非酒精性脂肪性肝病.     

水飞蓟宾脱氢衍生物的研究进展

2,3-脱氢水飞蓟宾是水飞蓟素中的有效成分之一,有比水飞蓟宾更强的抗氧化和抗肿瘤活性,本文综述了水飞蓟宾脱氢衍生物---2,3-脱氢水飞蓟宾的研究进展。     

水飞蓟素抗肝损伤及治疗糖尿病并发症作用的研究

主要综述近3年水飞蓟素、水飞蓟宾和水飞蓟宾-磷脂复合物在药理和临床上新的应用。这些化合物具有抗氧化、抗脂质过氧化、抗纤维化、抗炎症、细胞膜稳定、免疫调节和肝再生等活性。它们最常用作肝保护剂,也应用于拮抗糖化氧化和胰岛素增敏活性以及抗糖尿病、治疗非酒精性脂肪性肝病。     

水飞蓟宾-磷脂酰胆碱复合物与水飞蓟宾对四氯化碳所致小鼠急性肝损伤保护作用的对比

目的比较水飞蓟宾 磷脂酰胆碱复合物 (SPC)与水飞蓟宾对四氯化碳所致的小鼠肝损伤的保护作用。方法 5 0只小鼠随机分成 5组 ,通过对对照组、给药组小鼠血清中天冬氨酸氨基转移酶 (AST)、丙氨酸氨基转移酶(ALT)及肝组织学观察 ,比较SPC与水飞蓟宾对四氯化碳所致小鼠肝损伤之预防作用的效果。结果水飞蓟宾和SPC均能降低小鼠血清ALT、AST活性 ,能减轻肝脏病理学变化 ,但以SPC作用最为明显。结论SPC对四氯化碳造成的急性肝损伤有明显的保护作用 ,SPC的作用强于水飞蓟宾。     

Tetracyclines-extending the atypical spectrum

The main features and the present position of tetracyclines are reviewed. The mechanism of their action, bacterial resistance and the most recent findings are reported. Their decreased use is due to the availability of new, active, better-tolerated antibiotics. However, tetracyclines still have a place in the treatment of chlamydial and rickettsial infections, brucellosis and Lyme disease. In respiratory infections, they can be employed when necessary in infections caused by Chlamydia psittaci, C. pneumoniae, Mycoplasma pneumoniae, and also by Streptococcus pneumoniae and Haemophilus influenzae, whose rates of resistance now seem lower than in the past when tetracyclines were more largely prescribed.     

Therapeutic spectrum in the treatment of myelodysplastic syndromes

During the last 15 years, important progress has been made in the understanding of the biology and prognosis of myelodysplastic syndromes (MDS). It is a clonal disorder, characterised by ineffective haematopoiesis, which can lead to either fatal cytopenias or acute myelogenous leukaemias. Risk-adapted treatment strategies were established, due to the high median age (60 – 75 years) of the MDS patients and the individual history of the disease (i.e. number of cytopenias, cytogenetic changes, transfusion requirements). Allogeneic bone marrow transplantation currently offers the only potentially curative treatment, but this form of therapy is not available for the ‘typical’ MDS patient, who is > 60 years of age. Therapy with erythropoietin and granulocyte colony-stimulating factor has improved the quality of life of selected patients. The development of target-specific therapies, including antibodies and small molecules directed against specific molecular alterations in MDS, with minimal adverse effects, is the hope for the future. Furthermore, the innovative use of immunomodulatory agents and the optimising of cytotoxic treatment should continue to help in the treatment of MDS.     

Therapeutic spectrum in the treatment of myelodysplastic syndromes

During the last 15 years, important progress has been made in the understanding of the biology and prognosis of myelodysplastic syndromes (MDS). It is a clonal disorder, characterised by ineffective haematopoiesis, which can lead to either fatal cytopenias or acute myelogenous leukaemias. Risk-adapted treatment strategies were established, due to the high median age (60 - 75 years) of the MDS patients and the individual history of the disease (i.e. number of cytopenias, cytogenetic changes, transfusion requirements). Allogeneic bone marrow transplantation currently offers the only potentially curative treatment, but this form of therapy is not available for the 'typical' MDS patient, who is > 60 years of age. Therapy with erythropoietin and granulocyte colony-stimulating factor has improved the quality of life of selected patients. The development of target-specific therapies, including antibodies and small molecules directed against specific molecular alterations in MDS, with minimal adverse effects, is the hope for the future. Furthermore, the innovative use of immunomodulatory agents and the optimising of cytotoxic treatment should continue to help in the treatment of MDS.     

Calcium channel blockers in the spectrum of antihypertensive agents

Calcium channel blockers (CCBs) are widely used in the treatment of hypertension. Through blood pressure reduction, and possibly other mechanisms such as antioxidative effects, they may play a role in diminishing the risk for a variety of cardiovascular outcomes. The combination of CCBs with other newer antihypertensive agents such, as ACE inhibitors and angiotensin receptor blockers, may provide complementary effects on risk reduction in cardiovascular adverse events and renal disease. Although the efficacy of CCBs as antihypertensive agents has been adequately demonstrated, there have been concerns regarding the use of short acting dihydropyridines after acute myocardial infarction. There have also been questions about the role of CCBs with regards to other antihypertensive agents in renal disease. For example, differential effects of dihydropyridine and non-dihydropyridine CCBs may affect progression of renal disease and risk for diabetes. Certain precautions involving drug interactions are needed because of the effects of CCBs on the CYP450 enzyme systems.     

Calcium channel blockers in the spectrum of antihypertensive agents

Calcium channel blockers (CCBs) are widely used in the treatment of hypertension. Through blood pressure reduction, and possibly other mechanisms such as antioxidative effects, they may play a role in diminishing the risk for a variety of cardiovascular outcomes. The combination of CCBs with other newer antihypertensive agents such, as ACE inhibitors and angiotensin receptor blockers, may provide complementary effects on risk reduction in cardiovascular adverse events and renal disease. Although the efficacy of CCBs as antihypertensive agents has been adequately demonstrated, there have been concerns regarding the use of short acting dihydropyridines after acute myocardial infarction. There have also been questions about the role of CCBs with regards to other antihypertensive agents in renal disease. For example, differential effects of dihydropyridine and non-dihydropyridine CCBs may affect progression of renal disease and risk for diabetes. Certain precautions involving drug interactions are needed because of the effects of CCBs on the CYP450 enzyme systems.     

糖尿病湿性坏疽细菌感染菌谱及耐药菌谱特点研究

目的 明确糖尿病湿性坏疽感染菌谱和耐药菌谱特点,有针对性的选择抗菌药物。方法 取糖尿病湿性坏疽分泌物进行需氧菌、真菌培养、药敏试验以及厌氧菌培养。结果 357例患者中,细菌培养结果阳性率为100%,共培养出469株细菌,其中感染率革兰阳性菌(G+)45.4%、革兰阴性菌(G-)26.0%、厌氧菌23.7%、真菌4.9%。G+菌中葡萄菌属有5种药物的耐药菌株大于50%、肠球菌属有11种药物的耐药菌株大于50%,G-菌中肠杆菌科有3种药物的耐药菌株大于50%,不动杆菌属和假单胞菌属有8种药物的耐药菌株大于50%,真菌中光滑念珠菌有3种药物的耐药菌株大于50%,其余菌属药物的耐药菌株均小于50%。结论 糖尿病湿性坏疽感染菌谱特点是革兰阳性菌>革兰阴性菌、厌氧菌>真菌,耐药菌谱特点是G+菌感染中的肠球菌属、G-菌感染中的不动杆菌属和假单胞菌属、真菌感染中的光滑念珠菌耐药性较高。     

Effects of L-alpha-glycerylphosphorylcholine on the EEG power spectrum in the rat

The effects of L-alpha-glycerylphosphorylcholine (alpha-GPC), a putative acetylcholine precursor, on the EEG power spetrum in rats were investigated. The results show that the oral administration of alpha-GPC (100–300–600 mg/kg) induced a significant decrease in absolute spectral energy in the delta frequency band. A significant increase in absolute spectral energy in the beta frequency band was elicited by alpha-GPC at dose levels of 100 and 300 mg/kg, while the administration of a higher dose (600 mg/kg) of this compound resulted in the loss of response (bell-shaped dose-response curve). No significant changes in the EEG power spectrum were found in rats treated with phosphatidylcholine (PC). The present data, suggesting that the electrocorticographic (ECoG) activation elicited by alpha-GPC may be correlated with its stimulatory effect on brain acetylcholine release, further extend the pharmacological profile of this new cognition enhancer. © 1992 Wiley-Liss, Inc.     

Cardiovascular risk in the spectrum of type 2 diabetes mellitus

The clinical importance of the metabolic syndrome is that this group of risk factors greatly increases the likelihood of cardiovascular events, the major source of disease morbidity and mortality in patients with obesity and type 2 diabetes. Recent studies have helped clarify the mechanisms underlying the vascular dysfunction that leads to cardiovascular outcomes in diabetes. This vascular dysfunction is correlated with visceral adiposity, insulin resistance and alterations in the levels of a variety of circulating factors. The vascular effects of overt hyperglycemia also play an important role in diabetes mellitus. Appropriate management of diabetes in the context of the metabolic syndrome requires that we pay close attention to minimizing cardiovascular risk. In this brief review, we will cover several key concepts in the pathophysiology of type 2 diabetes that confer increased cardiovascular risk and influence the choice of oral therapies for this widespread disorder.     

Glutamate mediated signaling in the pathophysiology of autism spectrum disorders

Autism spectrum disorder (ASD) is a childhood neurodevelopmental disorder. During fetal and neonatal brain development, the cues for neurodevelopment are regulated in a well orchestrated manner. Generally, neurotransmitters play a major role in the formation of central nervous system (CNS) and peripheral nervous system (PNS). Glutamate, the excitatory neurotransmitter actively participates in various neurodevelopmental processes through complex regulatory events. Excitatory neurotransmitter signaling via glutamate receptors modulates cognitive functions such as memory and learning, which are usually impaired in ASD. Therefore, glutamate and its regulatory molecules are considered as potential targets for these disorders. Pharmacological, biochemical and behavioral studies reveal possible involvement of glutamatergic system in ASD pathology. An abnormal increase in electrical activity resulting from excessive glutamate signaling causes prolonged alterations in behavior, as commonly seen in ASDs. On the contrary, reports on animal models of hypoglutamatergia demonstrate phenotypes that overlap with features seen in autism. So controversies prevail whether to regard autism as hyper- or hypo-glutamatergic disorder. This paper reviews the role of glutamate and its regulatory proteins such as different receptors, transporters and metabolizing enzymes in the pathophysiology of ASD based on evidences gathered through multidisciplinary approaches. All these information raise the possibility of exploiting glutamatergic neurotransmitter system for future therapeutic interventions for ASD.