HPLC法同时测定苯磺酸氨氯地平片中7个杂质的含量

目的：探讨潞党参口服液对环磷酰胺所致的免疫抑制小鼠的免疫调节作用。方法：240只ICR小鼠随机均分6组：空白组、模型组、香菇多糖（0.2 g·kg-1）组和潞党参口服液低、中、高剂量组（3.3、6.6、13.2 g·kg-1）。连续3天腹腔注射环磷酰胺（50 mg·kg-1）建立免疫抑制小鼠模型，采用香菇多糖和潞党参口服液灌胃进行治疗14天，检测小鼠体质量、免疫器官脏器指数、血清溶血素、脾脏淋巴细胞增殖、腹腔巨噬细胞吞噬能力，以及血清免疫因子IL-2、IL-4和IFN-γ水平，研究潞党参口服液的免疫调节作用。结果：与空白组比较，模型组小鼠体质量、免疫器官脏器指数、血清溶血素水平、脾脏淋巴细胞增殖率、腹腔巨噬细胞吞噬能力以及血清免疫因子IL-2、IL-4和IFN-γ水平均显著降低（P<0.05，P<0.01）；潞党参口服液中、高剂量组和香菇多糖组治疗后，免疫抑制小鼠体质量、免疫器官脏器指数、血清溶血素水平、脾脏淋巴细胞增殖率、腹腔巨噬细胞吞噬能力及血清免疫因子IL-2、IL-4和IFN-γ水平均显著升高，与模型组比较具有统计学意义（P<0.05，P<0.01）。结论：潞党参口服液能够改善环磷酰胺所致免疫抑制小鼠的免疫功能。     

紫花牡荆素对佐剂性关节炎小鼠足肿胀度和细胞因子的影响

目的研究紫花牡荆素对佐剂性关节炎小鼠血浆炎症相关细胞因子的作用及其与足跖肿胀度的相关性。方法 36只Bal b/c小鼠,随机分为6组:空白对照组、模型组、阳性药物组、紫花牡荆素12.5,25.0和50.0mg·kg~(-1)剂量组;小鼠右足垫皮内注射弗氏完全佐剂后连续灌胃给药12d,每日1次。第13天测量小鼠后足爪的肿胀度,第14天采血,用流式细胞仪的微球阵列(CBA)法检测佐剂性关节炎小鼠外周血中的致炎性细胞因子(IL-2、IFN-γ和TNF-α)和抗炎性细胞因子(IL-4和IL-5)的水平。结果紫花牡荆素可剂量依赖性地抑制Bal b/c小鼠后足爪的肿胀度;明显降低致炎性Th1细胞因子IL-2、IFN-γ和TNF-α的水平,显著提高抗炎性Th2细胞因子IL-4和IL-5的水平;小鼠后足爪肿胀度与血清细胞因子IL-2、IFN-γ和TNF-α的水平呈正相关,与IL-4和IL-5的水平呈负相关。结论紫花牡荆素改善佐剂性关节炎小鼠足跖肿胀度,可能是通过增加血液IL-4和IL-5含量,降低IL-2、IFN-γ和TNF-α含量,调节细胞因子平衡的结果。     

短葶山麦冬多糖对免疫抑制小鼠的免疫功能的影响

目的研究短葶山麦冬多糖(LMP)对环磷酰胺致免疫低下小鼠的影响。方法应用环磷酰胺建立免疫低下小鼠模型,连续21天灌胃给予不同剂量(0.5、1.0、2.0g·kg-1)LMP后,测定小鼠胸腺指数、脾脏指数、腹腔巨噬细胞吞噬率、血清溶血素、细胞因子IL-2、TNF-α、IL-6含量、脾淋巴细胞增殖、NK细胞活性等免疫指标。结果 LMP能升高免疫低下小鼠胸脏指数,明显增加小鼠腹腔巨噬细胞吞噬率,增加血清溶血素和细胞因子(IL-2、TNF-α)含量,同时能明显提高脾淋巴细胞增殖能力和NK细胞活性。结论 LMP能够增强免疫抑制小鼠机体免疫功能。     

云南雀嘴茶对免疫功能低下小鼠的保护作用

目的 研究雀嘴茶的免疫调节作用。方法 取雄性ICR小鼠,制作环磷酰胺致免疫抑制小鼠模型,分别给予雀嘴茶及蒸馏水灌服,取血清。用酶联免疫吸附测定法(ELISA)测定小鼠血清的白细胞介素-2(IL-2)、γ-干扰素(IFN-γ)的含量,用流式细胞仪测定小鼠血清CD4,CD8,CD3的水平。用紫外法测定血清溶血素的含量。结果 雀嘴茶能够提高小鼠血清中CD4,CD8,CD3的百分比分别至(31.56±6.51)%,(11.47±3.63)%,(2.91±0.82)%,提高IL-2及IFN-γ的含量分别至(562.74±43.82)pg/L和(1 035.40±44.84)pg/L,提高溶血素的吸光度(OD)值至(1.380±0.159),与模型组相比,均有显著性差异(P<0.05或0.01)。结论 雀嘴茶具有提高小鼠免疫功能的作用。     

结核病人血清IL-17、TNF-α、IFN-γ的检测及其免疫学意义

目的:探讨白细胞介素17(IL-17)、肿瘤坏死因子α(TNF-α)及干扰素γ(IFN-γ)在结核病免疫机制中的作用。方法:采用ELISA法测定31例新发结核未治疗病人,25例结核治疗好转病人IL-17、TNF-α,IFN-γ水平,并用26例正常健康人作对照。结果:结核未治疗病人组血清IL-17、TNF-α明显高于对照组(P<0.01),结核治疗好转病人组血清IL-17、TNF-α则明显低于结核未治疗病人组(P<0.01)。结核未治疗病人组血清IFN-γ明显低于对照组(P<0.01),结核治疗好转病人组血清IFN-γ则明显高于结核未治疗病人组(P<0.01),结核未治疗病人组和结核治疗好转病人组IL-17与TNF-α呈正相关(r=0.6605,r=0.7605,P<0.001)。结论:人体感染结核杆菌后,IL-17增高,TNF-α升高,IFN-γ减低,炎症加重,可能引起免疫功能失衡,是导致结核病的发病因素之一,但经过治疗后,IL-17降低,TNF-α降低,IFN-γ升高,炎症反应减轻,病情趋于好转。     

槐白皮水提物对免疫抑制小鼠的免疫作用

目的 探讨槐白皮水提物对免疫抑制小鼠免疫功能的影响。方法 昆明小鼠随机分为正常组,模型组,香菇多糖组和槐白皮水提物低、中、高剂量组,除正常组外,其余各组连续3 d腹腔注射环磷酰胺复制免疫抑制模型。造模后连续灌胃给药14 d,血细胞计数仪测定小鼠外周血白细胞数目、称量并计算免疫器官系数、MTT法测定脾淋巴细胞增殖和NK细胞活性,ELISA检测血清IL-2、IFN-γ和TNF-α水平。结果 槐白皮水提物中、高剂量组明显提高免疫抑制小鼠的外周血白细胞水平和免疫器官系数,显著增加LPS诱导的脾淋巴细胞增殖,显著增强脾NK细胞活性,提高免疫抑制小鼠血清IL-2、IFN-γ水平;槐白皮水提物高剂量组明显提高ConA诱导的脾淋巴细胞增殖,显著提高免疫抑制小鼠血清TNF-α水平。结论 槐白皮水提物可以提高免疫抑制小鼠的免疫功能。     

原花青素对环磷酰胺致免疫抑制小鼠免疫功能的影响

目的 探究原花青素（PC）对环磷酰胺（Cy）致免疫抑制小鼠的免疫调节作用及其对白细胞介素-10（IL-10）、肿瘤坏死因子-α（TNF-α）表达的影响。方法 选用40只ICR小鼠，随机均分为正常对照组、Cy模型组、PC高剂量组（100 mg/kg）和PC低剂量组（80 mg/kg）。灌胃给药，7 d后测定各组小鼠胸腺（脾脏）指数、血清溶血素水平、迟发型超敏反应性；酶联免疫吸附测定（ELISA）检测外周血IL-10和TNF-α的表达；RT-qPCR测定小鼠脾脏TNF-α和IL-10 mRNA的表达。结果 PC能够提高小鼠胸腺、脾脏指数，一定程度恢复免疫抑制小鼠的迟发型超敏反应能力，提高血清溶血素含量；同时PC也可降低外周血IL-10的表达，升高TNF-α的表达；降低脾细胞IL-10 mRNA的水平，升高TNF-α mRNA的水平。结论 原花青素可以提升机体免疫功能，其调节机制可能是通过对细胞因子TNF-α和IL-10的调节来完成的。     

玄参多糖对正常生理小鼠和免疫低下状态小鼠免疫功能的影响

目的:考察玄参多糖对正常生理小鼠和免疫低下状态小鼠免疫功能的影响。方法:将80只小鼠随机分为正常组,模型组,治疗高、中、低剂量组和生理高、中、低剂量组,每组10只。正常组和模型组小鼠ig蒸馏水(10 mL/kg),治疗高、中、低剂量组和生理高、中、低剂量组均按0.16、0.08、0.04 g/kg ig给药,每天1次,连续7 d;于给药第3天开始,模型组和治疗高、中、低剂量组小鼠分别ip环磷酰胺(100 mg/kg),连续4 d,复制免疫低下模型。采用碳廓清实验测定小鼠碳廓清指数和脏器(胸、脾)指数。另取80只小鼠分组、给药同上,采用绵羊红细胞致敏后测定其血清半数溶血值(HC_(50))。再另取80只小鼠分组、给药同上,采用1%二硝基氟苯法诱导小鼠迟发型变态反应测定其耳肿胀度,测定其血清中白细胞介素(IL)-2、IL-4、血清免疫球蛋白G(IgG)、免疫球蛋白M(IgM)、γ-干扰素(IFN-γ)含量,并考察脾淋巴细胞的体外增殖情况。结果:高剂量玄参多糖可促进两种免疫状态下小鼠免疫器官及碳廓清指数的增长(P<0.05);增强小鼠迟发型变态反应的强度(HC_(50)值升高)(P<0.01)及改善模型小鼠血清溶血素含量的降低(P<0.01);促进脾淋巴细胞增殖(P<0.05)及升高血清中IL-2、IL-4、IgG、IgM、IFN-γ含量(P<0.05或P<0.01)。结论:玄参多糖可增强正常生理和环磷酰胺所致免疫低下两种状态下小鼠的免疫功能。     

玉郎伞多糖对体外BALB/C小鼠淋巴细胞和巨噬细胞分泌细胞因子的影响

目的:探讨玉郎伞多糖（YLSPS）体外对BALB/C小鼠淋巴细胞、巨噬细胞分泌肿瘤坏死因子-α（TNF-α）、白细胞介素-6（IL-6）、γ-干扰素（IFN-γ）及白细胞介素-2（IL-2）的影响及作用机制。方法:分离BALB/C小鼠腹腔巨噬细胞和脾淋巴细胞,分为空白对照组、LPS或ConA对照组和各浓度YLSPS组(50,100,200 mg·L^-1),MTT法检测脾淋巴细胞增殖,ELISA法检测细胞培养液中TNF-α、IL-6、IFN-γ、IL-2的浓度,RT-PCR法检测TNF-α、IL-6、IFN-γ、IL-2 mRNA的表达。结果:各浓度YLSPS组能剂量依赖性地促进BALB/C小鼠脾淋巴细胞增殖和TNF-α、IL-6、IFN-γ、IL-2的分泌,显著增强这些细胞因子的mRNA的表达（P<0.01或P<0.05）。结论:YLSPS体外能促进BALB/C小鼠脾淋巴细胞和腹腔巨噬细胞分泌IFN-γ、IL-2、TNF-α和IL-6,其作用机制可能与上调上述细胞因子mRNA表达有关。     

原发性高血压患者血压昼夜节律与细胞因子的相关性研究

目的探讨细胞因子与血压昼夜节律的相关性。方法将84例高血压病患者分为杓型组35例,非杓型组49例,分别测定血清肿瘤坏死因子-α(TNF-α)、白细胞介素-6(IL-6)、γ-干拢素(IFN-γ),集落刺激因子-1(CSF-1)水平。结果非杓型组与杓型组比较,TNF-α、IL-6、CSF-1明显升高,IFN-γ明显降低;血压夜间下降与IFN-γ正相关,与TNF-α、IL-6、CSF-1负相关。多元线性回归分析,TNF-α、IL-6、CSF-1与夜间血压下降直线相关。结论细胞因子参与原发性高血压患者血压昼夜节律调节     

Efficacy of gut lavage,hemodialysis, and hemoperfusion in the therapy of paraquat or diquat intoxication

Clinical and in vitro investigations were carried out to test the efficacy of gut lavage, hemodialysis, and hemoperfusion in the treatment of poisoning with paraquat or diquat. In a patient suffering from diquat intoxication 130 times more diquat was removed by gut lavage 30 h after ingestion than was removed by complete aspiration of the gastric contents.Determination of in vitro clearances for paraquat and diquat by hemodialysis showed that, at serum concentrations of 1–2 ppm, such as are frequently encountered in poisoning in man, toxicologically relevant quantities of herbicide cannot be removed from the body. At a concentration of 20 ppm, on the other hand, hemodialysis proved to be effective, the clearance being 70 ml/min at a blood flow rate of 100 ml/min. The efficacy of hemoperfusion with coated activated charcoal was on the whole better. Especially at concentrations around 1–2 ppm, the clearance values for hemoperfusion were some 5–7 times higher than those for hemodialysis.In a patient suffering from paraquat poisoning, both hemodialysis as well as hemoperfusion were carried out. The in vitro results could be confirmed: At serum concentrations of paraquat less than 1 ppm no clearance could be obtained by hemodialysis while by hemoperfusion with activated charcoal quite high clearance values were measured and the serum level dropped down to zero.

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Zusammenfassung Klinische Untersuchungen und Laboratoriumsversuche wurden durchgeführt, um die Wirksamkeit von Darmspülung, Hämodialyse und Hämoperfusion bei Paraquat- und Deiquat-Vergiftungen zu prüfen.Bei einem Patienten wurde 30 Std nach Deiquat-Aufnahme durch Darmspülung 130mal mehr Deiquat entfernt als durch vollständige Aspiration des Mageninhaltes. In vitro-Versuche ergaben, daß bei Blutserumkonzentrationen von 1–2 ppm, die bei Vergiftungen oft gemessen werden, durch Hämodialyse keine toxikologisch relevanten Paraquat- oder Deiquat-Mengen entfernt werden können. Dagegen erwies sich die Hämodialyse bei 20 ppm und einer Blutumlaufgeschwindigkeit von 100 ml/min mit einer Clearance von 70 ml/min als wirksam. Die Hämoperfusion mit beschicheter Aktivkohle war in diesen Versuchen aber eindeutig überlegen, denn insbesondere bei Konzentrationen um 1–2 ppm waren die Clearance-Werte 5–7mal höher als bei der Hämodialyse.Die in vitro-Ergebnisse wurden bei einem Patienten mit einer Paraquat-Vergiftung bestätigt: Bei Konzentrationen unter 1 ppm war die Hämodialyse wirkungslos, während durch Hämoperfusion relativ hohe Clearance-Werte erreicht wurden, so daß der Serumspiegel rasch unter die Nachweisgrenze abfiel.

     

In vitro studies on sterically stabilized liposomes (SL) as enzyme carriers in organophosphorus (OP) antagonism

This study describes a new approach for organophosphorous (OP) antidotal treatment by encapsulating an OP hydrolyzing enzyme, OPA anhydrolase (OPAA), within sterically stabilized liposomes. The recombinant OPAA enzyme was derived from Alteromonas strain JD6. It has broad substrate specificity to a wide range of OP compounds: DFP and the nerve agents, soman and sarin. Liposomes encapsulating OPAA (SL)* were made by mechanical dispersion method. Hydrolysis of DFP by (SL)* was measured by following an increase of fluoride ion concentration using a fluoride ion selective electrode. OPAA entrapped in the carrier liposomes rapidly hydrolyze DFP, with the rate of DFP hydrolysis directly proportional to the amount of (SL)* added to the solution. Liposomal carriers containing no enzyme did not hydrolyze DFP. The reaction was linear and the rate of hydrolysis was first order in the substrate. This enzyme carrier system serves as a biodegradable protective environment for the recombinant OP-metabolizing enzyme, OPAA, resulting in prolongation of enzymatic concentration in the body. These studies suggest that the protection of OP intoxication can be strikingly enhanced by adding OPAA encapsulated within (SL)* to pralidoxime and atropine.     

Aquatic Insects and Trace Metals: Bioavailability,Bioaccumulation, and Toxicity

Abstract

The uptake of metals from food and water sources by insects is thought to be additive. For a given metal, the proportions taken up from water and food will depend both on the bioavailable concentration of the metal associated with each source and the mechanism and rate by which the metal enters the insect. Attempts to correlate insect trace metal concentrations with the trophic level of insects should be made with a knowledge of the feeding relationships of the individual taxa concerned. Pathways for the uptake of essential metals, such as copper and zinc, exist at the cellular level, and other nonessential metals, such as cadmium, also appear to enter via these routes. Within cells, trace metals can be bound to proteins or stored in granules. The internal distribution of metals among body tissues is very heterogeneous, and distribution patterns tend to be both metal and taxon specific. Trace metals associated with insects can be both bound on the surface of their chitinous exoskeleton and incorporated into body tissues. The quantities of trace meals accumulated by an individual reflect the net balance between the rate of metal influx from both dissolved and particulate sources and the rate of metal efflux from the organism. The toxicity of metals has been demonstrated at all levels of biological organization: cell, tissue, individual, population, and community. Much of the literature pertaining to the toxic effects of metals on aquatic insects is based on laboratory observations and, as such, it is difficult to extrapolate the data to insects in nature. The few experimental studies in nature suggest that trace metal contaminants can affect both the distribution and the abundance of aquatic insects. Insects have a largely unexploited potential as biomonitors of metal contamination in nature. A better understanding of the physico-chemical and biological mechanisms mediating trace metal bioavailability and exchange will facilitate the development of general predictive models relating trace metal concentrations in insects to those in their environment. Such models will facilitate the use of insects as contaminant biomonitors.     

Alzheimer’s disease – current trends in basic and clinical research. Highlights from the 16th ECNP

Advances in the molecular biological knowledge of neuronal nicotinic acetylcholine receptors (nAChRs) have led to a growing interest by the pharmaceutical industry in the development of novel compounds that selectively modulate nAChR function. The ability of (-)-nicotine, an activator of nAChRs, to enhance attentional aspects of cognition in animals and humans, to exert neuroprotective and anxiolytic-like effects, and presumably to mediate the negative correlation between smoking and Alzheimer's (and Parkinson's) Disease, has focused interest on the potential therapeutic utility of modulators of nAChR function for treatment of some of the deficits associated with these progressive, neurodegenerative conditions. Numerous compounds are known which activate nAChRs and which might serve as lead compounds toward the development of such agents. The pharmacologic diversity of neuronal nAChR subtypes suggests the possibility of developing selective compounds which would have more favourable side-effect profiles than existing agents. This broader class of agents, collectively called cholinergic channel modulators (ChCMs), is anticipated to encompass compounds which would have more favourable side-effect profiles than existing agents, which generally exhibit low selectivity. This selectivity may be achieved by preferentially activating some subtypes of nAChRs (i.e., Cholinergic Channel Activators, ChCAs) or inhibiting the function of other subtypes (Cholinergic Channel Inhibitors, ChCIs). An overview of the biology of nAChRs and the rationale for the use of ChCMs for the treatment of dementia related to neurodegenerative diseases are presented, followed by a discussion of lead compounds and compounds under consideration for clinical evaluation.     

Steroidal sapogenin contents in some domestic plants

In order to find out the values of the steroid resources for the future use. the compositions and contents of steroidal sapogenins from 13 domestic plants have been investigated. As a result,Dioscorea nipponica, D. quinqueloba andSmilax china were found to have large amount of diosgenin. And pennogenin inTrillium kamtschaticum andParis verticillata, yuccagenin inAllium fistulosum, hecogenin inAgave americana and neochlorogenin inSolanum nigum were appeared to be major steroidal sapogenins.