Is the autophagy a friend or foe in the silver nanoparticles associated radiotherapy for glioma？

Malignant glioma is the most common intracranial tumor with a dismal prognosis. The radiosensitizing effect of silver nanoparticles (AgNPs) on glioma both in vitro and in vivo had been demonstrated in the previous studies of our group. However, the underlying mechanism is still unclear. Consistent with previous studies, a size and dose dependent antitumor effect and significant radiosensitivity enhancing effect of AgNPs were observed in our experiment system. We also found that cell protective autophagy could be induced by AgNPs and/or radiation, which was verified by the use of 3-MA. The mechanism through which had autophagy and the enhancement of radiosensitivity taken place was further investigated with inhibitors of ERK and JNK pathways. We demonstrated that ERK and JNK played pivotal roles in the radiosensitivity enhancement. Inhibiting ERK and JNK with U0126 and SP600125 respectively, we found that the autophagy level of the cells treated with AgNPs and radiation were attenuated. Moreover, SP600125 down-regulated the apoptosis rate of the co-treated cells significantly. Taken together, the present study would have important impact on biomedical applications of AgNPs and clinical treatment for glioma.     

Topography of median eminence somatostatinergic innervation

Somatostatin (SRIF) in the central nervous system is mostly concentrated in the median eminence (ME). Immunocytochemical methods have revealed high densities of SRIF-positive perikarya between the preoptic area and the periventricular nucleus of the hypothalamus (NPE). The aim of the present study was to define more precisely the specific pathways of SRIF neurons from NPE to the ME. SRIF levels were measured by radioimmunoassay, following various hypothalamic transections. Frontal periventricular sections decreased SRIF-ME content by 70% (P less than 0.01), when located at the anterior end of the ME but no diminution was observed when the cuts were located anteriorly or posteriorly. Parasaggital transections decreased SRIF-ME levels by 50% (P less than 0.05) when located at the outer border of the ventromedial and premammillary nucleus, but the decrease was not significant when cuts were located anteriorly. Taken together, our data indicate that most SRIF-containing neurons, originating in the NPE, do not reach the ME directly along the border of the 3rd ventricle; instead they form a loop across the medial forebrain bundle before re-entering the mediobasal hypothalamus at the ME level.     

Somatosensory nuclei in the brainstem of the rat: independent projections to the thalamus and cerebellum

The dorsal column nuclei and the sensory trigeminal nuclei project not only to the ventrobasal thalamus but also to the cerebellum. In this study the numbers and distribution of neurones projecting to these two regions were examined for the following nuclei: the rostral part of the main cuneate nucleus, the external cuneate nucleus, nucleus x, the principal sensory nucleus of the trigeminal nerve, and the oral, interpolar, and caudal subnuclei of the spinal nucleus of the trigeminal nerve. A thalamic projection from nucleus x and from the external cuneate nucleus was confirmed, and a distinct group of neurones projecting to the ventroposteromedial thalamus was distinguished near the ventromedial aspect of the principal sensory nucleus. Of the 165,000 neurones examined, only one was found to be double labelled. It was concluded that the populations of neurones that project to the ventrobasal thalamus and to the cerebellum are separate, and that somatosensory neurones in the brainstem do not send axon collaterals to both regions.     

p38丝裂原活化蛋白激酶信号级联在炎症反应中的作用

在急、慢性疾病中，细胞释放的炎症介质可以活化多种信号转导级联反应，丝裂原活化蛋白激酶(MAPK)信号转导通道在招募白细胞于炎症部位聚集起着重要的作用。同时，p38MAPK异构体的活化可以激活致炎细胞因子，而后刺激白细胞活化。然而，p38MAPK引起的白细胞招募这一系列的功能过程包括：粘附、游走和效应器的功能如氧化爆发以及p38MAPK介导的复杂细胞因子网络在炎症中的作用仍有待研究。针对减少炎症介质产生和以p38MAPK为治疗靶点的研究正在进行中，不远的将来可能会成为治疗炎症疾病的新策略。     

17β-雌二醇对子宫内膜异位症患者在位子宫内膜间质细胞β-catenin mRNA和蛋白表达的影响

目的研究17β-雌二醇(17β-E2)对子宫内膜异位症(内异症)患者在位子宫内膜间质细胞β-catenin mRNA和蛋白表达的影响,探讨Wnt/β-catenin信号通路在介导雌激素促进内异症发生发展的作用。方法体外分离培养内异症患者在位子宫内膜间质细胞。用不同浓度17β-E2处理子宫内膜间质细胞48 h;此后选用10-10mol/L 17β-E2处理子宫内膜间质细胞12、24和48 h,逆转录聚合酶链反应(RT-PCR)和免疫印迹法(Western blotting)检测17β-E2处理前后子宫内膜间质细胞β-catenin mRNA和蛋白的表达水平。同法分析雌激素受体拮抗剂ICI182,780(10-6mol/L)对17β-E2促进β-catenin mRNA和蛋白表达的影响。免疫组织化学染色观察17β-E2作用后β-catenin在子宫内膜间质细胞中的定位。结果17β-E2能明显促进内异症患者在位子宫内膜间质细胞β-catenin mRNA和蛋白的表达,并呈剂量和时间依赖性,于10-10mol/L作用48 h最明显。雌激素受体拮抗剂ICI182,780能明显抑制17β-E2对子宫内膜间质细胞β-catenin mRNA和蛋白的表达。免疫组织化学染色发现17β-E2能促进β-catenin在子宫内膜间质细胞核内的表达。结论雌激素可能通过激活Wnt/β-catenin信号通路促进内异症在位子宫内膜的异位种植。     

Voltage-Gated calcium channels and nonvoltage-gated calcium uptake pathways in the rat incisor odontoblast plasma membrane

Odontoblasts participate actively in the transport and accumulation of Ca²⁺ ions to the mineralization front during dentinogenesis. These cells are known to carry membrane-bound ATP-driven pumps and Na⁺/Ca²⁺ antiports for Ca²⁺ extrusion, but little is known about Ca²⁺ influx mechanisms into these cells. It has been shown that the administration of Ca²⁺ channel blockers in vivo strongly impairs Ca²⁺ uptake in the mineral phase during dentinogenesis in the rat; the present in vitro study is aimed at further elucidating odontoblast Ca²⁺ uptake mechanisms. Dissected rat incisor odontoblasts exhibited a pronounced fluorescence when incubated with a fluorescently-labeled (STBodipy) dihydropyridine, which is specific for voltage-gated Ca²⁺ channels of the L-type, and this binding was competitively abolished by nifedipine. As assayed by fluorescence spectrometry, odontoblast Ca²⁺ uptake was enhanced by the agonistic dihydropyridine BAYK-8644 (5 μM) as well as by plasma membrane depolarization in a high K⁺ (120 mM) medium. The Ca²⁺ uptake after depolarization was impaired by nifedipine (5 μM). When treated with the Ca²⁺-ATPase inhibitor cyclopiazonic acid (CPA; 10 μM), a nonvoltage-gated uptake of ⁴⁵Ca²⁺ was identified. This uptake was not influenced by nifedipine (20 μM) but was impaired by lanthanum ions (200 μM). A nonvoltage-gated uptake of Mn²⁺ into CPA-treated cells could be traced using the fura-2 quenching technique. This CPA-induced Ca²⁺ flux was not caused by an alteration of the plasma membrane potential, as assayed with di-8-ANEPPS. The results demonstrate that Ca²⁺ flux into dentinogenically active odontoblasts occurs through voltage-gated Ca²⁺ channels of the L-type and by nonvoltage-gated, agonist-sensitive Ca²⁺ uptake pathways. Received: 6 November 1995 / Accepted: 21 February 1996     

Managed mental health care: problems and possibilities

Case management has become an established organizational approach to mental health care. However, a recent development of case management, known as 'managed care' has received only limited attention in the UK and this has been confined to acute medical or surgical hospital care. The potential of managed care as applied to mental health care is uncertain. This paper clarifies the nature of managed care and discusses its relevance to mental health care, in particular to the care of people suffering from schizophrenia. The high incidence and heavy resource demands of this user group makes these people an ideal focus for managed care. However, there are conceptual and practical problems hindering its development and implementation, including: the variability and unpredictability of the disease process of schizophrenia; challenges of outcome measurement; and problems relating to the current organization of mental health care.     

视交叉后损害的临床与图形视觉诱发电位分析

图形视觉诱发电位(P—VEP)是眼接受图形的刺激时,视路及大脑皮质枕区所产生的一系列电位变化。在视交叉后病变的诊断,病情估计及预后推测中有比较肯定的价值。 本文对17例视交叉后损害的病人进行分析。发现视交叉后病变以视皮质损害为主,表现为视物模糊,视力下降,视野改变。P—VEP检查的异常率与病变部位大小及病变性质有关。同时检查半视野刺激有助于提高阳性率。     

Chromatic pattern-reversal electroretinograms (ChPERGs) are spared in multiple system atrophy compared with Parkinson’s disease

Abstract Idiopathic Parkinson’s disease (IPD) patients have abnormal visual evoked potentials (VEPs) and pattern electroretinograms (PERGs), attributed to dopaminergic transmission deficiency in visual pathway, probably the retina. VEP abnormalities are not reported in multiple system atrophy (MSA). The aim of this study was to investigate and compare chromatic (Ch) red-green (R-G) and blue-yellow (B-Y), and luminance yellow-black (Y-Bk) PERGs in patients with MSA and IPD. We investigated 6 MSA patients (mean age: 62±7.4 years) not undergoing any pharmacological treatment, as well as 12 early IPD patients (mean age: 60.1±8.3 years) and 12 age-matched normal observers. ChPERGs were recorded monocularly in response to full-field equiluminant R-G, B-Y and Y-Bk horizontal gratings. In MSA only responses to R-G stimuli showed minimal insignificant changes (slight but not significant amplitude reduction without any significant latency delay); no significant abnormality was detected for B-Y and luminance Y-Bk stimuli. By contrast, in IPD all responses were reduced in amplitude and delayed in latency, above all for B-Y stimuli. Present data indicate that both chromatic and achromatic PERGs are virtually unaffected in MSA, whereas in early IPD they are clearly impaired, suggesting different pathogenic retinal mechanisms and a useful simple tool for distinguishing MSA from IPD.