Effects of psychotropic agents on the physical properties of platelet membranes in vitro

Normal platelet membranes were exposed in vitro to a variety of psychotropic medications commonly used in the treatment of patients with psychiatric disorders. Changes in structural order at the hydrocarbon region of the drug-exposed membranes were determined by steadystate fluorescence polarization measurements employing the fluorescent probe 1,6-diphenyl-1,3,5-hexatriene (DPH). Chlorpromazine, an aliphatic phenothiazine, produced a significant increase in DPH fluorescence polarization at concentrations from 2–200 M. Thioridazine, a piperidine phenothiazine, and three piperazine derivatives, perphenazine, trifluoperazine, and fluphenazine, produced significant increases in this parameter at concentrations from 20–200 M. The other agents tested, including thiothixene, lithium, antidepressants, anxiolytics, and anticonvulsants, were without effect in the concentration ranges examined. The phenothiazine-induced increase in DPH fluoresence polarization apparently depended on the structure of the phenothiazine nucleus; changes in side-chain structure appeared to modulate this effect, most likely by altering the inherent membrane solubility of the agents.     

Experimental neurotoxicity of the anorectic fenfluramine

Summary Fenfluramine, an amphophilic compound which is a halogenated derivative of amphetamine, is still used as an anorectic agent for weight reduction, as it acts on the satiety center of the hypothalamus. Holtzman strain rats aged 6 days were daily injected s.c. fenfluramine hydrochloride at the dose of 75 mg/kg body weight. The animals were killed at different time intervals between days 7 and 40, and different parts of the brain were examined by light and electron microscopy. About half of the animals showed intralysosomal membrano-cytoplasmic bodies in the oligodendroglia, neurons, and neuropil, maximally in the animals receiving 8–19 injections. They were seen as concentrically arranged, single-layered lamellae; small dense bodies; or larger heterogeneous bodies. The mechanism of production of such inclusions could be the formation of complexes of this amphophilic compound with tissue phospholipids, or some enzyme-inhibiting action. A marked prominence of dark cells, predominantly oligodendroglia, was also noticed in the brains of experimental animals. Some of these cells appeared to be dark neurons, probably resulting from the serotonin-depleting effect of fenfluramine. A few dark cells were identified as resting microglial cells, while macrophagic reactive microglia were detected in the brains of very young animals. Fenfluramine appears to provide a model for studying neuroglial reactions.Paper presented at the Erwin Riesch symposium on Lysosomal Disorders of the Nervous System, Berlin (Convenor, Prof. Cervos-Navarro); and as poster-talk at the 9th International Congress of Neuropathology, Vienna, September 1982     

淫羊藿醇提物调节M2样巨噬细胞极化减少乳腺癌细胞迁移和集落形成的研究

目的 探讨淫羊藿Epimedium brevicornu醇提物对体外巨噬细胞极化调控机制及对M2样巨噬细胞促进4T1细胞迁移和集落形成的影响。方法 采用CCK-8法检测不同浓度淫羊藿醇提物对骨髓来源巨噬细胞（bonemarrowderived macrophages,BMDM）活力的影响,确定淫羊藿醇提物的安全作用浓度;采用Western blotting和q RT-PCR检测淫羊藿醇提物对M2样巨噬细胞标志物精氨酸酶-1(arginase-1,Arg-1)和CD163表达的影响;采用q RT-PCR检测淫羊藿醇提物对M2-肿瘤相关巨噬细胞（tumor-associated macrophages,TAMs）相关基因炎症区域1(found in inflammatory zone 1,Fizz1)、过氧化物酶体增殖物激活受体γ(peroxisome proliferator-activated receptor γ,PPARγ)、几丁质酶3样分子3(chitinase 3-like 3,Ym1)、趋化因子24(C-C motif chemokine ligand 24,CCL24)、巨...     

急性脑梗塞的红细胞膜流动性及生化指标改变

目的 探讨急性脑梗塞（ＡＣＩ）的发病机制及治疗措施。方法 采用测定ＡＣＩ患者血浆粘度,纤维蛋白原含量,红细胞膜荧光偏振度Ｐ,过氧化脂质水平,超氧化物歧化酶活性等指标进行对比研究。结果 与同龄健康组比较,ＡＣＩ患者ηｐ,Ｆｇ,ＬＰＯ水平均显著升高,ＳＯＤ活性显著降低。红细胞膜流动性下降。     

Rapid appearance of β-amyloid precursor protein immunoreactivity in glial cells follwing excitotoxic brain injury

Clinical and experimental data have indicated an up-regulation of amyloid precursor protein (APP) after various types of CNS injury. In the present study the cellular source of lesion-induced APP has been investigated an a neurotoxic CNS model. Quinolinic acid injection into the striatum results in neuronal degeneration, while glial cells survive. APP immunoreactivity was detected in glial cells starting at postoperative day 3 and persisted until day 21, the last time point studied. Double immunocytochemistry identified the majority of APP-immunoreactive cells as glial fibrillary acidic protein-immunoreactive astrocytes. There was no evidence of amyloid fibril deposition during this time. It is concluded that following excitotoxic neuronal degneration APP is mainly produced by reactive astrocytes in the lesioned area.     

Selective localization of gelatinase A,an enzyme degrading β-amyloid protein,in white matter microglia and in Schwann cells

Gelatinase A is an enzyme capable of cleaving soluble -amyloid protein (AP), and may function as an -secretase to produce secretory forms of amyloid precursor protein. We examined gelatinase A immunoreactivity in the brains and posterior roots of neurologically normal, lacunar stroke, Alzheimer disease (AD), amyotrophic lateral sclerosis, progressive supranuclear palsy and myasthenia gravis cases. The gelatinase A antibody stained only microglial cells in the white matter in all the brain tissues. In AD brain, the reactive microglia located in the center of classical senile plaques, as well as in other microglial cells in the gray matter, showed no immunoreactivity. Gelatinase A in white matter microglial cells may play a role in preventing local deposition of AP. In the posterior root, Schwann cells had positive immunoreactivity. As with other metalloproteases, gelatinase A in Schwann cells may play an antiproliferative role.     

Fluorescence automatic cell sorter and immunohistochemical investigation of CD68-positive cells in meningioma

Infiltration of brain neoplasms by mononuclear cells including monocytes/macrophages has attracted little attention since they have marked morphological heterogeneity. Twenty-seven meningiomas were studied by anti-CD68 antibody-gated flow cytometry and by immunohistochemical analysis using the anti-CD68 antibodies. Flow cytometric analysis divided cells contained within tumor tissues into CD68-positive and -negative cells. In addition, eight gliomas, eight metastatic brain tumor, and 12 pituitary adenomas were investigated in the same way to compare meningiomas. The mean contents of CD68-positive cells were 24.0±3.7% in meningiomas, 4.4±1.4% in gliomas, 9.5±3.9% in metastatic brain tumors, and 4.5±1.8% in pituitary adenomas. Immunohistochemically, CD68-positive cells showed significant heterogeneity and were detected as round, rod-shaped, ameboid and ramified cells in meningiomas. Although the infiltrated mononuclear cells in gliomas have been investigated to some degree and showed that they express cytokines and/or growth factors, these infiltrated cells in meningioma have barely been studied. The CD68-positive cells detected in this study are likely to be monocytes, macrophages and microglias, and are presumed to be in various functional stages and to play important roles in growth regulation in meningioma.     

蔗糖对红细胞膜脂流动性测定稳定性的影响

研究蔗糖对测定红细胞膜脂流动性稳定性的影响。应用荧光偏振技术测定膜脂流动性,并对比其在单纯悬浮液和含0．25mol／L蔗糖悬浮液中的测定结果的变异系数。结果在含有蔗糖悬浮液中测得结果的变异系数要比单纯悬浮液中的小3～5倍。结果表明,加入蔗糖对膜脂流动性的测定具有稳定性作用。     

Dielectric Analysis of Phosphorylcholine Head Group Mobility in Egg Lecithin Liposomes

Purpose. A knowledge of the interfacial properties of lecithin underpins our understanding of many of the physicochemical characteristics of drug delivery systems such as liposomes and lecithin stabilized microemulsions. In order to further this understanding, a high frequency dielectric study of the interfacial properties of egg lecithin liposomes was undertaken. Methods. The effect of temperature, lecithin concentration and probe sonication on the interfacial dielectric properties of liposomal suspensions was investigated by high frequency dielectric relaxation spectroscopy between 0.2–6 GHz. Results. The frequency dependent permittivity of each suspension exhibited a dielectric dispersion centred around 100 MHz, corresponding to the relaxation of zwitterionic head groups. The activation energy for head group reorientation was estimated as H = 6.3 kJ mol^–1. There was an increase in extent of inter-head group interactions on increasing the liposome volume fraction, whereas the effect of probe sonication showed that: (i) head groups in both the outer and inner lamellae contribute to the dielectric response; (ii) the head groups may be less restricted in liposomes of high surface curvature with few lamellae; (iii) the high frequency permittivity of the suspension increased on sonication, as a result of a reduction in the amount of (depolarized) interlamellar water following a reduction in the number of lamellae per liposome. Conclusions. Dielectric analysis of the zwitterionic head groups of lecithin therefore provides a means for investigating the surface of lecithin liposomes, and may be used to investigate the effect of drugs and other solutes on membranes.     

Time-resolved confocal fluorescence microscopy of porphyrins for phototherapy

The application of a novel time-resolved confocal fluorescence microspectrometer to studies of the distribution and speciation of porphyrin photosensitizers in rat C6 cerebral glioma cells is described. The instrument combines a mode-locked argon ion laser excitation source with time-correlated single photon counting fluorescence detection and has sub-micron spatial and sub-nanosecond temporal resolution. The porphyrins studied were haematoporphyrin derivative (HpD), haematoporphyrin IX (HP), porphyrinc (Pc) and the tetrakiscarborane carboxylate ester of 2,4-(,-dihydroxyethyl) deuteroporphyrin IX (BOPP). From the heterogeneous emission observed in vitro, assignments and spatial location of various porphyrin species are proposed.