白芍总苷对胶原诱导性关节炎大鼠长期给药的组织分布研究

目的 研究白芍总苷的主要成分芍药苷、芍药内酯苷对胶原诱导性关节炎（collagen-induced arthritis,CIA）大鼠长期给药后的组织分布。方法 建立超高效液相色谱串联质谱（UPLC-MS/MS）法,测定白芍总苷长期给药后大鼠心、肝、脾、肺、肾、小肠、胸腺、滑膜等组织中芍药苷和芍药内酯苷的分布情况。结果 长期给药后,芍药苷和芍药内酯苷主要分布于小肠和肾,其次为脾、胸腺、滑膜、肝、肺、心。2种成分在CIA大鼠中的组织分布大多低于正常大鼠。结论 揭示了白芍总苷长期给药后的组织分布特征,为探讨白芍总苷治疗类风湿性关节炎的靶器官以及疗效的改进提供了参考。     

TrkC Is Essential for Nephron Function and Trans-Activates Igf1R Signaling

BackgroundInjury to kidney podocytes often results in chronic glomerular disease and consecutive nephron malfunction. For most glomerular diseases, targeted therapies are lacking. Thus, it is important to identify novel signaling pathways contributing to glomerular disease. Neurotrophic tyrosine kinase receptor 3 (TrkC) is expressed in podocytes and the protein transmits signals to the podocyte actin cytoskeleton.MethodsNephron-specific TrkC knockout (TrkC-KO) and nephron-specific TrkC-overexpressing (TrkC-OE) mice were generated to dissect the role of TrkC in nephron development and maintenance.ResultsBoth TrkC-KO and TrkC-OE mice exhibited enlarged glomeruli, mesangial proliferation, basement membrane thickening, albuminuria, podocyte loss, and aspects of FSGS during aging. Igf1 receptor (Igf1R)–associated gene expression was dysregulated in TrkC-KO mouse glomeruli. Phosphoproteins associated with insulin, erb-b2 receptor tyrosine kinase (Erbb), and Toll-like receptor signaling were enriched in lysates of podocytes treated with the TrkC ligand neurotrophin-3 (Nt-3). Activation of TrkC by Nt-3 resulted in phosphorylation of the Igf1R on activating tyrosine residues in podocytes. Igf1R phosphorylation was increased in TrkC-OE mouse kidneys while it was decreased in TrkC-KO kidneys. Furthermore, TrkC expression was elevated in glomerular tissue of patients with diabetic kidney disease compared with control glomerular tissue.ConclusionsOur results show that TrkC is essential for maintaining glomerular integrity. Furthermore, TrkC modulates Igf-related signaling in podocytes.     

反复呼吸道感染儿sIL－2R和T细胞亚群的测定

本文采用双抗体夹心ＥＬＩＳＡ法分别测定了２１例反复呼吸道感染儿，３０例正常儿童，１０例新生儿脐血的血清可溶性白细胞介素２受体（ｓＩＬ＝２Ｒ）水平。结果患儿组ｓＩＬ－２Ｒ为７１６．６０±３０．１０Ｕ／ｍｌ；正常儿童组为３８４．４７±８８．０３Ｕ／ｍｌ（ｐ＜０．０１）；新生儿脐血为４４６．２０±５５．６８Ｕ／ｍｌ，与正常儿童比较Ｐ＞０．０５。同时采用间接免疫荧光技术测定了患儿Ｔ细胞亚群水平，结果ＣＤ８细胞数升高，ＣＤ３细胞和ＣＤ４细胞数、ＣＤ４／ＣＤ８比值下降，与正常儿童比较有显著性差别。提示反复呼吸道感染儿有细胞免疫功能降低及免疫调节紊乱。     

SLE患者淋巴细胞膜上IL-2R表达的动态分析

本实验采用Wu Tac单克隆抗体的间接荧光抗体法,动态观察了系统性红斑狼疮(SLE)患者和正常供血员(对照组)的外周血淋巴细胞经PHA刺激后,于不同时间(0、24、48、72小时)内细胞膜上白细胞介素2受体(IL-2R)的表达。结果表明在给予PHA刺激培养24、48和72小时后,与对照组比较SLE患者淋巴细胞的IL-2R表达明显下降,提示了SLE的T淋巴细胞反应性降低可能与被激活的T细胞表面IL-2R的表达功能缺陷有关。此结果将有助于进一步探讨SLE的免疫调节紊乱的发生机制。     

恶性肿瘤患者血清sIL—2R的检测

本文采用ELISA夹心法,对66例恶性肿瘤患者血清中可溶性白细胞介素2受体进行检测,以39例健康学生做对照,结果显示恶性肿瘤患者血清slL-2R 含量明显高于对照组(P<0.01)。并对血清sIL-2R 水平在肿瘤诊断及预后判断中的意义进行了探讨。     

Human Peripheral Eosinophils with Receptors for IgM: Demonstration and Ultrastructural Morphology

Receptors for IgM were detected on peripheral blood human eosinophils by a rosette technique with ox red blood cells coated with the IgM fraction of the specific immunserum. Between 14 % and 43 % (mean 27 %) FcµR positive cells were found after an overnight incubation period at 37°C by using this technique. The specificity of the receptors for IgM was assessed by studying the inhibitory capacity of purified human IgM in the rosette assay. From an ultrastructural point of view, the EA^M rosette-forming cells are mature eosinophlic granulocytes characterized by a nucleus with a variable number of lobes and a certain number of «first type» granules partially or totally devoid of their content.     

A TLC screening program for 170 commonly used pesticides using the corrected Rf value (R f c value)

Summary This article reports TLC data (corrected R_f values; R _f ^c values) of 170 commonly used pesticides which are regularly encountered in toxicological analysis. Silica gel was used as the stationary phase and three binary systems were chosen as solvents.     

Prejunctional inhibition of sympathetically evoked pupillary dilation in cats by activation of histamine H3 receptors

Summary Frequency-dependent pupillary dilations were evoked by electrical stimulation of the pre- or post-ganglionic cervical sympathetic nerve (sympatho-excitation) or the hypothalamus (parasympatho-inhibition) in sympathectomized anesthetized cats. Systemic administration of the selective histamine H₃ receptor agonist (R)--methylhistamine (RMeHA) produced a dose-dependent depression of mydriasis due to direct neural sympathetic activation but had no effect on responses elicited by parasympathetic withdrawal. The histamine H₂ receptor agonist, dimaprit, was inactive. RMeHA was much more effective in depressing sympathetic responses obtained at lower frequencies when compared to higher frequencies of stimulation.Responses evoked both pre- and postganglionically were inhibited by RMeHA. This peripheral sympathoinhibitory action of RMeHA was antagonized by the histamine H₃ receptor blocker thioperamide but not by intravenous pretreatment with the histamine H₁ receptor antagonist chlorpheniramine. Histamine H₂ receptor blockers cimetidine and ranitidine were also without effect. RMeHA did not depress pupillary responses elicited by i.v. (-)-adrenaline.The results demonstrate that histamine H₃ receptors modulate sympathetic activation of the iris at a site proximal to the iris dilator muscle. The predominant mechanism of action appears to the prejunctional inhibition of noradrenaline release from postganglionic sympathetic nerve endings. However, a concomitant ganglionic inhibitory action cannot be excluded. Correspondence to M. C. Koss at the above address     

Hemodynamic differences between carvedilol and labetalol in the cutaneous circulation

The effects of labetalol and carvedilol on local cutaneous microvascular perfusion and calculated local cutaneous microvascular resistance were investigated in anesthetized rats at submaximal doses that produced equivalent reductions in blood pressure and heart rate. Labetalol decreased cutaneous perfusion (– 25% ± 3%) without significantly affecting cutaneous vascular resistance ( – 6% ± 3%). In marked contrast, carvedilol dramatically increased cutaneous perfusion ( + 64% ± 9%) and significantly reduced cutaneous vascular resistance ( – 57% ± 3%). These results suggest that carvedilol and labetalol possess differences in the mechanisms by which they produce vasodilation in vivo.     

Schedule dependent potentiation of antitumor drug effects by α-difluoromethylornithine in human gastric carcinoma cells in vitro

A clone of human gastric cancer cells (AGS-6) and the parental line (AGS-P) from which it was isolated were used in cell survival studies to determine whether pretreatment for 24, 48 or 72h with -difluoromethylornithine (DFMO, 5mM) would increase the cell's sensitivity to 5-Fluorouracil (5FU), Adriamycin (Adria), 1-(2-chloroethyl)-3-(4-methyl cyclohexyl)-1-nitrosourea (MeCCNU), or Bleomycin (Bleo). Generally, the AGS parental cells were most sensitive to the anticancer agents after exposures to DFMO. However, there was no way to predict in advance from DFMO-induced changes in ornithine decarboxylase (ODC), polyamine or cell kinetics values, how long an exposure to DFMO was required before sensitization to an anticancer agent occurred. The degree of potentiation for a single drug was variable from time to time during exposure to DFMO, and broad differences in the sensitizations were demonstrated among the four anticancer drugs. The AGS-6 clone exhibited little or no increased sensitivity as a result of pretreatment with DFMO, even though the DFMO-induced reductions in ODC and polyamine values in these cells were similar to those produced in the more sensitive parental line.