甲壳低聚糖的制备和分析

解决壳聚精的水不溶性,拓宽壳聚精的应用范围。方法：直接用过氧化氢对高分子量、高脱乙酸化度的壳聚糖进行非均相降解、制备了水溶性甲壳低聚糖产品,对产品进行红外光谱结构表征,并用高效毛细管电泳测定了寡糖的聚合度。探讨了温度、过氧化氢浓度对降解所需时间、产品得率及甲壳低聚糖聚合度的影响。结果：选择降解温度 ８０℃～９０℃,过氧化氢浓度 ８％～１０％时,水解时间０．５ ～１．０ ｈ,水溶性产品得率为 ４０％～４５％,聚合度为３～７的寡糖占水解产物的３６％～５０％。结论：该方法制备甲壳低聚糖是可行的。如进一步研究工艺条件,有望进行工业化生产。     

壳聚糖衍生物对异丙肾上腺素诱导的H9c2心肌损伤的保护作用

目的 探究5种壳聚糖衍生物对大鼠心肌细胞的保护作用。方法 在5种壳聚糖衍生物对大鼠心肌细胞H9c2的细胞形态学和生长增值研究基础上,通过建立H9c2细胞异丙肾上腺素损伤模型,研究5种壳聚糖衍生物对损伤H9c2细胞的保护作用。结果 N-乙酰氨基葡萄糖、磺酸化壳寡糖、低脱乙酰度壳寡糖、高脱乙酰度壳寡糖、羧甲基壳聚糖均能不同程度地促进H9c2细胞的生长,对损伤H9c2细胞均有保护和增殖促进作用,N-乙酰氨基葡萄糖、磺酸化壳寡糖、低脱乙酰度壳寡糖、高脱乙酰度壳寡糖的最佳作用浓度均为50 μg?mL-1,羧甲基壳聚糖的最佳作用浓度为100 μg?mL-1。     

壳聚糖及其衍生物在医药领域的应用研究进展

壳聚糖又称壳糖胺、几丁聚糖等，为天然多糖甲壳素（聚-1，4-β-N-乙酰-2-氨基-2-脱氧-D-葡萄糖）脱除部分乙酰基的产物。根据脱M乙酰度和溶解性的不同，一般将N-脱乙酰度〈55%不溶于1％乙酸（或1％盐酸）的称为甲壳素，将N-脱乙酰度〉55％可溶于1％乙酸（或1％盐酸）的产物称为壳聚糖。一般有实际应用价值的壳聚糖N-脱乙酰度都在70％以上。壳聚糖的相对分子质量虽因制备方法不同从数十万到数百万不等，     

壳寡糖的分离分析及其诱抗活性研究

生物活性测定证明,壳寡糖的诱抗活性与壳寡糖的聚合度及脱乙酰度密切相关,低聚合度(DP<15)及高脱乙酰度的壳寡糖的诱抗活性高。本文采用高效液相色谱(HPLC)法和飞行时间质谱(TOF-MS)法检测壳寡糖的聚合度和脱乙酰度。     

壳聚糖微球的研究进展

壳聚糖是天然聚合物甲壳素脱乙酸基产物，具有独特的物理化学及生物学特征，是制备缓释、控释制剂较理想的高分子材料，已引起人们的广泛兴趣。本文综述壳策糖微球的制各方法，影响壳聚糖微球的制备及药物释放的因素，以及壳聚糖微球的作用特点等。     

甲壳素的理化研究 Ⅰ.分子量的测定

为测定甲壳素的分子量,本文首先在温和条件下将其脱乙酸化制得壳聚糖,然后用粘度法测定壳果糖的分子量,基于二者聚合度基本一致,推导出甲壳素分子量约为1×10~6。     

传统抗凝剂肝素的其它治疗作用

肝素及硫酸乙酸肝素（HS）在氨基葡聚精族中存在很大生物学差异。1肝素及HS的化学组成和细胞定位HS及肝素链常发软附干核蛋白中心的丝氨酸残基上。化学合成的肝素是D－葡糖酵酸呈1，4与，乙酸－D－氨基葡聚糖连接的二糖交替连接物。修改后的生物合成程序是：（1）N－乙酸－D－氨基葡聚糖脱乙酸化后，此氨基重新硫酸化；（2）D－葡糖醛酸C5差向异构化为L－艾杜糖醛酸；（3）主要在L－艾杜糖醛酸和D一氨基葡聚糖残基上的CZ及C6位氧一硫酸化2（4）在D一葡糖醛酸和D一氨基葡糖残基上的C。及C3位氧分别一硫酸化则是次要的。HS生物合成…     

壳聚糖降低人血脂、血小板粘附率及血沉率的作用

壳聚糖(Chitosan)是一种氨基多糖,可视为聚氨基葡萄糖或甲壳质(Chitin)的脱乙酰基衍生物,自然存在于动植物的结构组织中,形成细胞壁和骨骼成份。临床所用壳聚糖是以浓矸高温处理从海蟹壳和虾壳得到的甲壳质脱乙酰基而制得。     

补肾强精颗粒剂的药效学研究

目的对具有温肾助阳、补肾育精、和血补气、回春固本作用的补肾强精颗粒剂进行有关的男性不育症药效学研究。方法以肉苁蓉、制何首乌、海龙、狗鞭、仙茅、菟丝子、补骨脂等10味中药组成的补肾强精颗粒剂为试验材料,采用乙酸棉酚造模大鼠研究其对精子生成、精子活率及其活力的作用,试验其药效作用。结果补肾强精颗粒剂可显著地增加乙酸棉酚造模大鼠精子数量、精子活率及其活力,并能增强精子对毛细管的穿透能力。体外试验证明,可直接提高豚鼠精子活力及其受精能力。结论该方剂具有一定的补肾助阳功能,使用该方剂可用于治疗因少精子症、弱精子症和少精子伴弱精子症所致的男性不育症。     

补肾强精颗粒剂的药效学研究

目的对具有温肾助阳、补肾育精、和血补气、回春固本作用的补肾强精颗粒剂进行有关的男性不育症药效学研究。方法以肉苁蓉、制何首乌、海龙、狗鞭、仙茅、菟丝子、补骨脂等10味中药组成的补肾强精颗粒剂为试验材料,采用乙酸棉酚造模大鼠研究其对精子生成、精子活率及其活力的作用,试验其药效作用。结果补肾强精颗粒剂可显著地增加乙酸棉酚造模大鼠精子数量、精子活率及其活力,并能增强精子对毛细管的穿透能力。体外试验证明,可直接提高豚鼠精子活力及其受精能力。结论该方剂具有一定的补肾助阳功能,使用该方剂可用于治疗因少精子症、弱精子症和少精子伴弱精子症所致的男性不育症。     

A benzodiazepines derived compound, 4-(3-chlorophenyl)-1,3-dihydronaphtho [2,3-b][1,4]diazepin-2-one (ND700C), inhibits fMLP-induced superoxide anion release by activating protein phosphatase 2A in human neutrophils

We studied the mechanism underlying the inhibitory effect of a benzodiazepines derivative, 4-(3-chlorophenyl)-1,3-dihydronaphtho [2,3-b][1,4]diazepin-2-one (ND700C), on superoxide anion production induced by formly-methionyl-leucyl-phenylalanine (fMLP) in human neutrophils. ND700C inhibited the fMLP-induced superoxide anion production and cathepsin G release in a concentration-dependent manner with respective IC50 values of 5.0+/-0.5 and 8.7+/-0.8muM. In addition, ND700C was found to suppress fMLP-induced intracellular calcium mobilization and the phosphorylation of ERK and Akt. In another study, ND700C was observed to cause a rapid increase in intracellular cAMP level by up to threefold. Furthermore, when H89 was used to inhibit cAMP-dependent protein kinase A (PKA), we discovered that ND700C's suppressive effects on calcium mobilization, phosphorylation, and superoxide anion production were abrogated. ND700C demonstrated additive effect on the PGE1-induced increase in cAMP. However, this additive effect was not demonstrated with the IBMX-induced rise in cAMP. Our results indicated that ND700C did not directly inhibit the activity of phosphodiesterase 4. In another set of experiments, calyculin A and okadaic acid (both protein phosphatase 2A inhibitors) were found to reverse ND700C's positive effect on cAMP level. This observation suggested the involvement of protein phosphatase 2A in ND700C's cAMP-elevating mechanism. We found that the activity of protein phosphatase 2A was activated by ND700C. Furthermore, protein phosphatase 2A was co-immunoprecipitated with phosphodiesterase 4 after ND700C treatment in human neutrophils. Conclusion: ND700C inhibited fMLP-induced superoxide anion production through a PKA-dependent pathway. ND700C increased cAMP by activating protein phosphatase 2A, which subsequently inhibited phosphodiesterase 4.     

多肽ND100的抗肿瘤活性研究

目的　研究多肽ND100的抗肿瘤活性。方法　用液相法人工合成了抗肿瘤八肽ND100,分子量为 846 9。测定了ND100对 3种小鼠移植性肿瘤的抑制作用,并研究了ND100对小鼠红细胞和白细胞数量的影响。结果　体内抑瘤试验表明,ND100对小鼠H22肝癌、小鼠Lewis肺癌和小鼠S180肉瘤的生长均有明显抑制作用,有效剂量为 2 5mg·kg-1,当使用高剂量时(15mg·kg-1 )时,对 3种小鼠移植性肿瘤的抑制率达 0 70以上,且具有剂效关系。ND100对小鼠红细胞和白细胞的数量均无影响。结论　ND100具有明显的体内抗肿瘤活性。     

A benzodiazepines derived compound, 4-(3-chlorophenyl)-1,3-dihydronaphtho [2,3-b][1,4]diazepin-2-one (ND700C), inhibits fMLP-induced superoxide anion release by activating protein phosphatase 2A in human neutrophils

We studied the mechanism underlying the inhibitory effect of a benzodiazepines derivative, 4-(3-chlorophenyl)-1,3-dihydronaphtho [2,3-b][1,4]diazepin-2-one (ND700C), on superoxide anion production induced by formly-methionyl-leucyl-phenylalanine (fMLP) in human neutrophils. ND700C inhibited the fMLP-induced superoxide anion production and cathepsin G release in a concentration-dependent manner with respective IC₅₀ values of 5.0 ± 0.5 and 8.7 ± 0.8 μM. In addition, ND700C was found to suppress fMLP-induced intracellular calcium mobilization and the phosphorylation of ERK and Akt. In another study, ND700C was observed to cause a rapid increase in intracellular cAMP level by up to threefold. Furthermore, when H89 was used to inhibit cAMP-dependent protein kinase A (PKA), we discovered that ND700C’s suppressive effects on calcium mobilization, phosphorylation, and superoxide anion production were abrogated. ND700C demonstrated additive effect on the PGE₁-induced increase in cAMP. However, this additive effect was not demonstrated with the IBMX-induced rise in cAMP. Our results indicated that ND700C did not directly inhibit the activity of phosphodiesterase 4. In another set of experiments, calyculin A and okadaic acid (both protein phosphatase 2A inhibitors) were found to reverse ND700C’s positive effect on cAMP level. This observation suggested the involvement of protein phosphatase 2A in ND700C’s cAMP-elevating mechanism. We found that the activity of protein phosphatase 2A was activated by ND700C. Furthermore, protein phosphatase 2A was co-immunoprecipitated with phosphodiesterase 4 after ND700C treatment in human neutrophils. Conclusion: ND700C inhibited fMLP-induced superoxide anion production through a PKA-dependent pathway. ND700C increased cAMP by activating protein phosphatase 2A, which subsequently inhibited phosphodiesterase 4.     

Peripheral participation of cholecystokinin in the morphine-induced peripheral antinociceptive effect in non-diabetic and diabetic rats

The effects of cholecystokinin (CCK-8) and the CCK receptor antagonist proglumide, on antinociception induced by local peripheral (subcutaneous) injected morphine in non-diabetic (ND) and streptozotocin-induced diabetic (D) rats, were examined by means of the formalin test. Morphine induced dose-dependent antinociception both in ND and D rats. However, in D rats, antinociceptive morphine potency was about twofold less than in ND rats. Pre-treatment with CCK-8 abolished the antinociceptive effect of morphine in a dose-dependent manner in both groups of rats. Additionally, proglumide enhanced the antinociceptive effect induced by all doses of morphine tested. Both CCK-8 and proglumide had no effect on flinching behaviour when given alone to ND rats. Unlike ND rats, in D rats proglumide produced dose-dependent antinociception and CCK-8 enhanced formalin-evoked flinches, as observed during the second phase of the test. In conclusion, our data show a decrease in peripheral antinociceptive potency of morphine when diabetes was present. Additionally, peripheral CCK plays an antagonic role to the peripheral antinociceptive effect of morphine, additional to the well known CCK/morphine interaction at spinal and supraspinal level.     

ND与TD方案治疗非小细胞肺癌临床疗效对比研究

目的：比较和评价诺维本加顺铂（ND）与特素加顺铂（TD）联合化疗治疗晚期非小细胞肺癌的临床疗效及副反应。方法：79例晚期非小细胞肺癌分为ND组40例,TD组39例。化疗方案：ND组：NVB25mg/m^2,IV,D1.5,DDP35mg/m^2,IV,D1-3。TD组：特素135mg/m^2,静滴,D1,DDP35mg/m^2,IV,D1-3。结果：ND组CR＋PR20例,有效率50％,缓解期4－11月,中位缓解期6．5月。TD组CR＋PR16例,有效率41％,缓解期3．5－10月。中位缓解期6月。两组中位生存期分别为11月和10月,一年生存率分别为43％及36％（P＞0．05）。两组主要副反应为骨髓抑制,Ⅲ-Ⅳ度粒细胞减少ND组明显高于TD组（P＜0．01）,ND组另一副反应为静脉炎,TD组有1例高敏反应,其它副反应 无明显差异。结论：ND与TD方案治疗晚期非小细胞肺癌临床疗效无显著差异,副反应均可耐受,但ND组骨髓抑制及静脉炎发生率均明显高于TD组,TD组高敏反应问题临床应用中应引起重视。     

Childhood Adversity Increases Risk for Nicotine Dependence and Interacts with α5 Nicotinic Acetylcholine Receptor Genotype Specifically in Males

The relative importance of specific genetic and environmental factors in regulating nicotine dependence (ND) risk, including the effects on specific forms of childhood adversity on smoking risk, have been understudied. Genome-wide association studies and rodent models have demonstrated that the α5 nicotinic acetylcholine receptor gene (CHRNA5) is important in regulating nicotine intake. Childhood adversity increases the methylation level of the CHRNA5 promoter region in European Americans (EAs), an effect that was observed only in males (Zhang et al, submitted for publication). In view of this potential sex difference in the effects of early life experience on smoking, we investigated the presence of a sex-specific gene-by-environment effect of this marker on ND risk. A nonsynonymous SNP in CHRNA5 previously associated to ND and several related traits, rs16969968, was genotyped in 2206 EAs (1301 men and 905 women). The main and interactive effects of childhood adversity and rs16969968 genotype on diagnosis of ND and ND defined by dichotomized Fagerstrom test for ND (FTND) scores were explored. Men and women were analyzed separately to test for sex differences. Childhood adversity significantly increased ND risk in both sexes, and the effect in women was twice than that in men. Significant interactive effects of childhood adversity and rs16969968 genotype were observed in men (ND: OR=1.80, 95% CI=1.18–2.73, P=0.0044; FTND: OR=1.79, 95% CI=1.11–2.88, P=0.012). No interaction was found in women. This study provides evidence of a sex-specific gene × environment effect of CHRNA5 and childhood adversity on the risk for ND.     

Antioxidant effect of nimodipine in young rats after pilocarpine-induced seizures

Nimodipine (ND) is a centrally active calcium antagonist that blocks the voltage-dependent L-type channels. Its antiepileptic properties have been proved in various animal models, including pilocarpine-induced seizures in adult rats. In order to investigate protective effects of the ND (10 (ND10) and 30 mg/kg (ND30), i.p.), young male rats (21-day-old) received ND injections before pilocarpine administration (400 mg/kg, s.c., pilocarpine group (P400)). The pretreatment with ND10 and ND30 prolonged the latencies of seizures and death on this seizure model. ND pretreatment in two doses decreased the levels of lipid peroxidation when compared to pilocarpine group. The P400 administration increased the striatal catalase activity. However, the administration of ND, in dose of 30 mg/kg, 30 min before pilocarpine, preserved catalase activity in normal levels. On the other hand, no change was detected in the animals treated with the dose of 10 mg/kg. Our results confirm the neuroprotective effect of ND on the seizures in young rats, suggesting that this drug acts positively on lipid peroxidation. Our observations shows that nimodipine cannot induces these effects via blockade of Ca(2+)-channel.     

低频电刺激联合早期康复训练治疗急性脑梗死

目的:探讨双乳突法头部低频电刺激及早期康复训练对急性脑梗死患者神经功能缺损程度及日常生活能力(ADL)恢复的影响。方法:90例急性脑梗死患者,随机分为低频电刺激及早期康复训练组(A组)、低频电刺激组(B组)和对照组(C组),每组30例。A、B两组均采用低频电刺激、常规药物治疗,A组在发病48h内立即进行早期康复训练,分别观察治疗前后神经功能缺损评分及ADL的变化。结果:三组在治疗前神经功能缺损评分、ADL评分差异均无统计学意义(P<0.05),A组治疗后神经功能缺损评分、ADL评分明显好于B组及对照组,差异有统计学意义(P<0.01)。结论:低频电刺激及早期康复训练对急性脑梗死患者具有明显的临床疗效。     

Severity of hyperlipidemia does not affect antiatherosclerotic effect of an angiotensin II receptor antagonist in apolipoprotein E-deficient mice

The purpose of this study was to clarify whether severity of hyperlipidemia affects the antiatherosclerotic effect of angiotensin II receptor blockers (ARBs). The effect of olmesartan medoxomil, an ARB, on atherosclerotic lesion was examined in apolipoprotein E-deficient (ApoEKO) mice fed a normal diet (ND) or a high-fat-supplemented diet (FD) for 25 weeks. ApoEKO mice have high plasma cholesterol levels, which were further increased by feeding of an FD. Both the atherosclerotic lesion area of the aortic luminal surface and the atherosclerotic lesion thickness in the aortic valves were significantly greater in the FD mice than in the ND mice. Olmesartan medoxomil did not affect the plasma cholesterol levels in either the ND or FD ApoEKO mice; however, it reduced effectively both the atherosclerotic lesion surface area and the lesion thickness even in FD ApoEKO mice. It is concluded that the antiatherosclerotic effect of ARBs is not weakened by the high plasma cholesterol level, suggesting the usefulness of ARBs in the treatment of atherosclerosis, even in a situation in which the plasma cholesterol level is not fully controlled.     

Nanodisks derived from amphotericin B lipid complex

The goal of this study was to determine the effect of apolipoproteins on Amphotericin B lipid complex (ABLC). We report that incubation of ABLC with recombinant human apolipoprotein A-I (apoA-I) induces solubilization of ABLC by transforming the micron sized phospholipid/AMB assemblies into discrete nanoscale disk-shaped complexes termed nanodisks (ND). ApoA-I induced changes in ABLC solubility and morphology were monitored by spectroscopy and electron microscopy. AMB efficacy was evaluated in yeast and pathogenic fungi growth inhibition assays and the effect of AMB formulation on cell toxicity was assessed in cultured Hep3B cells. AMB associated with ND were more efficiently nebulized than AMB associated with ABLC. Thus, transformation of ABLC into ND preserves the potent biological activity of AMB as well as the reduced toxicity of the ABLC formulation. ABLC derived AMB-ND offer advantages over conventional ABLC in terms of stability, storage, nebulization efficiency and provides an intrinsic "handle" for tissue specific targeting via genetic engineering of its protein component.