尾吊大鼠胃窦部胃泌素,生长抑素,5—羟色胺和嗜铬颗粒素A免…

为深入探讨失重对胃肠内分泌功能的影响，用免疫组织化学ＡＢＣ染色法结合图象分析技术，研究了悬吊模拟失重大鼠胃窦部胃泌素（Ｇａｓ）、生长抑素（ＳＳ）、５－羟色胺（Ｔ－ＨＴ）和嗜铬颗粒素Ａ（ＣｇＡ）免疫反应（－ＩＲ）细胞的密度和灰度变化。结果显示，悬吊大鼠胃窦部Ｇａｓ－ＩＲ细胞的密度与灰度均较对照鼠减低。由于ＳＳ与Ｇａｓ和５－ＨＴ在功能上具有拮抗作用，因而表明，模拟失重状态下，胃窦部内分泌功能稳态可能有     

悬吊大鼠胃窦部和十二指肠5—HT免疫反应细胞的变化

为了探讨失重因素对胃肠5-羟色胺免疫反应(5-HT-IR)细胞的影响,我们用免疫组织化学ABC 法,对地面模拟失重大鼠和正常对照大鼠胃窦部和十二指肠的5-HT-IR 细胞进行了观察。结果表明,模拟失重大鼠胃幽门部及十二指肠各段的5-HT-IR 细胞均较对照大鼠明显增多。本文对这一结果及其意义进行了初步讨论。     

地面模拟微重力大鼠胃窦部和十二指肠生长抑素免疫反应细胞的变化

为了探讨模拟微重力状态下胃肠道生长抑素免疫反应细胞的变化规律,我们用肠卷石蜡切片的免疫组织化学ABC(Avidin Biotin—Peroxidase Complex tech-nique)法,对地面模拟微重力大鼠胃窦部和十二指肠的生长抑素免疫反应细胞进行了初步的观察,并与正常对照动物做了比较。结果表明,微重力动物胃窦部和十二指肠的生长抑素免疫反应细胞较对照动物明显减少。并讨论了这一现象及其与微重力引起的内分泌变化的相互关系。     

模拟失重大鼠胃窦黏膜白细胞介素2和生长抑素表达的变化

目的　研究模拟失重状态下大鼠胃窦部白细胞介素 2 (IL 2 )及生长抑素 (SS)免疫反应细胞的变化。　方法　采用尾部悬吊模拟失重 ,将大鼠分为悬吊 14d组、2 8d组及相应同步对照组。以免疫组织化学方法 ,观察大鼠胃窦部黏膜IL 2及SS免疫反应细胞的变化。　结果　与正常对照组相比 ,14d尾部悬吊大鼠胃窦部黏膜IL 2免疫反应细胞有下降趋势 ,但统计学分析无明显差异 ,SS免疫反应细胞减少 (P <0 0 1) ;2 8d尾部悬吊大鼠胃窦部黏膜IL 2和SS免疫反应细胞均明显减少(P <0 0 1)。　结论　在模拟失重状态下 2～ 4周 ,大鼠胃窦部的IL 2及SS的表达即可出现下降。     

30d尾吊大鼠血循环、肌肉和骨骼系统的变化

目的 确定中长期失重防护措施研究的模拟失重动物模型。方法 比较对照组鼠（ｎ＝１５）和尾吊鼠（ｎ＝１５）在实验３０ｄ后血循环,肌肉和骨骼系统的变化。结果 尾吊可引起血液流变性和红细胞变形能力下降,肌肉萎缩,肌肉收缩功能下降,肌纤维的Ⅰ型纤维向Ⅱ纤维转化,Ｌ３骨矿盐含量下降,股骨载荷功能降低和骨代谢变化。结论 尾吊鼠可作为今后研究的模拟失重动物模型。     

尾吊大鼠骨骼肌线粒体钙、镁含量和体视学的变化

为探讨尾吊大鼠骨骼肌线粒体Ｃａ２＋，Ｍｇ２＋离子含量、体视学变化与肌肉功能降低的关系，采用ＳＤ雄性大鼠５０只，体重１８０～２２０ｇ，按体重配对随机分为对照组和尾吊组。尾吊组３０只，－２５°；对照组２０只。尾吊第１５ｄ（１５只），第３０ｄ（１５只）断头，取比目鱼肌、腓肠肌冷冻待测试。采用差速离心分离线粒体，按Ｌｏｗｒｙ方法［１］测线粒体蛋白，钙、镁含量。按北京医科大学面分析方法测线粒体体视学各指标［２］。尾吊１５、３０ｄ大鼠比目鱼肌、腓肠肌线粒体Ｃａ、Ｍｇ含量与对照比增加，体视学各指标均有不同程度的改变。结果表明，尾吊后大鼠骨骼肌线粒体Ｃａ、Ｍｇ离子代谢和体视学均发生改变，其变化必然影响肌肉收缩功能。     

尾吊大鼠心肌组织局部肾素-血管紧张素系统的表达变化

目的 观察模拟失重对大鼠心肌组织局部肾素-血管紧张素系统（renin-angiotensin system,RAS）主要成份基因和蛋白表达的影响。方法 采用尾吊模拟失重影响,应用反转录-聚合酶链式反应（RT-PCR）和western印迹分析技术分别检测心肌组织基因和蛋白表达。结果 尾吊1周后,心肌组织血管紧张素原（angiotensinogen,AGT）、血管紧张素转化酶（angiotensin converting enzyme,ACE）、血管紧张素ⅡⅠ型受体1a亚型（AT1a）和1b亚型（AT1b）的基因和蛋白表达均无明显变化。尾吊4周后,AGTmRNA表达及AGT蛋白高分子量条带表达均显著增加（P〈0．05）,AGT蛋白低分子量条带表达却无明显改变;AT1a的mRNA表达显著增高（P〈0．05）,但其蛋白表达却没有明显变化。结论 4周尾吊后,大鼠心肌组织局部RAS主要成份表达增强,可能与失重／模拟失重后心肌纤维化程度增高有关。     

强肌Ⅰ、Ⅱ号中药改善尾吊大鼠比目鱼肌血流量和肌肉力学特性的作用

航天员因失重而产生肌肉萎缩,引起了国内外很多学者的关注,并进行了广泛研究。本文观察尾吊大鼠服用中药后比目鱼肌血流量和肌肉力学特性的变化。实验采用45只SD 品系雄性大鼠,体重240-300g,将鼠按体重分为3组。尾吊大鼠头低位20-25°。三组鼠每天按固定时间分别灌水和强肌Ⅰ、Ⅱ号中药(30g/kg),悬吊15天后,用戊巴比妥钠(4mg/100g)麻醉,用张力、位移传感器测量肌肉力学特性各参数,用标有~(51)Cr 同位素青蛙红血球方法测比目鱼肌的血流量。结果表明:强肌Ⅰ、Ⅱ号中药对尾吊大鼠比目鱼肌血流量、肌肉力学特性有改善作用。其中强肌Ⅱ号效果更明显。比目鱼肌的血流量与等长单收缩、强直收缩张力峰值呈正相关,相关系数分别为0.81、0.84。本结果为防护肌肉萎缩措施提供了实验依据。     

中药复方对尾吊大鼠心肌ATP酶、SDH和能荷值的影响

目的观察中药复方对短期模拟失重 (尾吊 )大鼠心肌ATP酶、SDH和能荷值的影响。方法大鼠分对照组、尾吊组和中药组 (中药 +尾吊 ) ,每组 1 0只。尾吊 5d后 ,3组大鼠同时处死 ,取心肌测ATP酶和SDH ,酶不同染色处理并定量测其光密度 (OD) ,测心肌能荷值定量表示能量储备。结果尾吊组心肌细胞SDH染色比中药、对照组增强 ,OD值升高 ,ATP酶明显增强和OD值显著升高 ,心肌能荷值减少 ,其顺序为尾吊组 >对照组 >中药组。结论中药组在尾吊时由于中药复方发挥了镇静、安神、活血化瘀等药理作用 ,使大鼠心肌SDH活性减弱 ,ATP酶活性明显降低 ,能耗减少     

Somatostatin receptor SPECT

Somatostatin is a peptide with a broad distribution in the nervous system and acts as a neurotransmitter in several organs, having a wide range of mainly inhibiting effects, such as the suppression of growth hormone release, as well as the inhibition of pancreatic and gastrointestinal hormone release. Five somatostatin receptor subtypes have been cloned and demonstrated to have an emphasized expression in all human tumours. In particular, type 2 receptors were identified as the most frequently represented on the surface of neuroendocrine tumour cells, providing the molecular basis for many clinical applications of somatostatin analogues. Towards the end of the 1980s, the in vivo demonstration of somatostatin receptors on the surface of some tumours raised interest in receptor imaging, and indeed the peptide receptor overexpression on tumour cells, as compared to normal tissues, constitutes the basis for molecular imaging of these tumours. This review intends to illustrate the development of single photon emission radiopharmaceuticals for the study of somatostatin receptors and their application in diagnostic imaging.     

Somatostatin receptor imaging

[(111)In-DTPA(0)]octreotide is a radiopharmaceutical with a great potential for the visualization of somatostatin receptor-positive tumors. The overall sensitivity of Somatostatin Receptor Imaging (SRI) to localize neuroendocrine tumors is high. In a number of neuroendocrine tumor types, as well as in Hodgkin's disease, inclusion of SRI in the localization or staging procedure may be very rewarding, either in terms of cost-effectiveness, patient management, or quality of life. The value of SRI in patients with other tumors, like breast cancer, or in patients with granulomatous diseases, has to be established. The development of Peptide Receptor Radionuclide Therapy (PRRT) is expected to stimulate peptide receptor imaging.     

Somatostatin analogue scintigraphy in granulomatous diseases

Normal as well as activated lymphocytes and macrophages have previously been shown by radioreceptor analysis to express somatostatin receptors (SS-R). The somatostatin (SS) analogue [¹¹¹In-DTPA-d-Phe¹]octreotide (¹¹¹In-octreotide) is already used successfully in the visualization of a variety of neuro-endocrine tumours and malignant lymphomas. In the present study 20 consecutive patients were investigated, 12 with sarcoidosis, one with both sarcoidosis and aspergillosis, four with tuberculosis and three with Wegener's granulomatosis. For in vivo SS-R imaging, total-body scintigraphy was performed 24 and 48 h after the administration of ¹¹¹In-octreotide. Granuloma localizations could be visualized in all patients studied; additional sites were found in nine patients with sarcoidosis and in two patients with tuberculosis. In vitro autoradiography of fresh tissue biopsies, using the SS analogue [¹²⁵I-Tyr³]octreotide, showed binding at sites that were microscopically identified as granulomatous inflammation. These observations demonstrate the expression of SS-R by human granulomas. This scintigraphy procedure may contribute to a more precise staging and evaluation of granulomatous diseases, but more importantly it may be a sensitive indicator of the efficacy of glucocorticoid and/or immunosuppressive therapy.     

Somatostatin receptor imaging in intracranial tumours

The somatostatin analogue [¹¹¹In-DTPA-d-Phe¹]-octreotide (¹¹¹In-octreotide) allows scintigraphic visualization of somatostatin receptor-expressing tissue. While it is well known that a large variety of tissues express somatostatin receptors and ¹¹¹In-octreotide scintigraphy has a clearly defined role in various neuroendocrine diseases, the clinical value of ¹¹¹In-octreotide scintigraphy in brain tumours is still under clinical investigation. In 124 patients with 141 brain lesions (63 meningiomas, 24 pituitary adenomas, 10 gliomas WHO class I and II, 12 gliomas WHO class III and IV, 11 neurinomas and 2 neurofibromas, 7 metastases and 12 other varieties: three non-Hodgkin B-cell lymphomas, two epidermoids, one abscess, one angioleiomyoma, one chordoma, one haemangiopericytoma, one osteosarcoma, one plasmacytoma and one pseudocyst), ¹¹¹In-octreotide scintigraphy was performed 4–6 and 24 h after i.v. injection of 110–220 MBq ¹¹¹In-octreotide. Planar images of the head in four views with a 128×128 matrix and single-photon emission tomographic images (64×64 matrix) were acquired, and lesions were graded according to qualitative tracer uptake. Fifty-nine of the 63 meningiomas showed moderate to intense tracer uptake. Nine of 24 pituitary adenomas were visible; the remaining 15 did not show any tracer uptake. None of the class I and II gliomas with an intact blood-brain barrier were detected whereas 11/12 class III and IV gliomas showed ¹¹¹In-octreotide uptake. None of the neurinomas or neurofibromas were positive. Five of seven metastases were classified as positive, as were the osteosarcoma, two of three non-Hodgkin B-cell lymphomas, one abscess, one angioleiomyoma, one chordoma and one haemangiopericytoma. The other varieties (one non-Hodgkin B-cell lymphoma, two epidermoids, one plasmacytoma and one pseudocyst) did not show ¹¹¹In-octreotide uptake. The results demonstrate that a large variety of intracranial lesions express somatostatin receptors and therefore can be visualized by [¹¹¹In-DTPA-d-Phe¹]-octreotide scintigraphy. This technique can be valuable in the differentiation between meningiomas and pituitary adenomas, based on qualitative tracer uptake. [¹¹¹In-DTPA-d-Phe¹]-octreotide scintigraphy allows differentiation between meningiomas and neurinomas or neurofibromas and therefore provides complementary information to computed tomography or magnetic resonance imaging. Furthermore, this technique allows differentiation between scar tissue and recurrent meningiomas postoperatively and can help in non-invasive tumour differentiation of multiple intracranial lesions, which can be of value in defining the most adequate therapeutic strategy. Received 1 December 1997 and in revised form 17 March 1998     

Somatostatin analogue scintigraphy in carcinoid tumours

Scintigraphy with iodine-123 or indium-111 labelled somatostatin analogue (octreotide) was performed in 52 patients diagnosed as, suspected of, or at risk of having carcinoid tumours. In 32 of 37 (86%) patients in whom histologically proven carcinoids were still present, known tumour sites were visualized. Using ¹²³I-coupled octreotide, 24 of 40 (60%) known extrahepatic sites were visualized, whereas all of 12 (100%) extrahepatic lesions were visualized after injection of ¹¹¹In-coupled octreotide. Known liver metastases were not distinctly visualized with octreotide scintigraphy in 12 of 24 patients. In all but two of these cases, an even distribution of radioactivity in the liver was observed. This is most probably due to the fact that these liver metastases accumulated about as much radioactivity as does normal liver tissue. Previously unsuspected localizations or sites not recognized with other imaging techniques were found in 20 of the 37 patients. In 3 of 11 patients who were thought to have been surgically cured, and in 4 of 4 patients who were suspected of having carcinoids, octreotide scintigraphy showed abnormal accumulation of radioactivity. Histological or radiological evidence that additional sites noticed on octreotide scintigrams indeed represented tumour tissue was obtained in ten patients. Visualization of the carcinoids did not depend on the site of the tumour or on the presence or absence of hormonal hypersecretion, as measured by urinary 5-hydroxyindoleacetic acid and serum -subunit concentrations. Apart from its use for tumour localization, octreotide scintigraphy, in consequence of its ability to demonstrate somatostatin receptor positive tumours, could be used to select those patients with the carcinoid syndrome who are likely to respond favourably to octreotide treatment.Correspondence to: D.J. Kwekkeboom     

Somatostatin receptor scintigraphy for bronchial carcinoid follow-up

PURPOSE: Somatostatin receptor scintigraphy (SRS) has been used to diagnose bronchial carcinoids (BC) and is a valuable tool for accurate staging of BC. The aim of this study was to evaluate the role of SRS in restaging BC and following patients after treatment. METHODS: Thirty-one patients (18 male, 13 female) with confirmed BC who were referred during the last 7 years were included. Patients were examined via chest radiograph (12 studies), chest or abdominal computed tomography (CT; 28 scans), chest magnetic resonance imaging (2 scans), and liver ultrasound (5 scans). RESULTS: Overall, in 22 patients (71%), SRS confirmed the data obtained by other diagnostic procedures (16 negative and 6 positive findings). In 6 patients, SRS showed focal lesions not previously demonstrated. In 2 patients, SRS resolved uncertain findings of CT. In 1 patient, SRS showed fewer lesions compared with CT. In 8 of 31 patients, important diagnostic information obtained by SRS was not revealed by any other imaging procedure. CONCLUSION: Our results indicate that SRS is a reliable, noninvasive method that could be considered the principal follow-up procedure in patients with BC.     

Somatostatin receptor-mediated imaging and therapy: basic science, current knowledge, limitations and future perspectives

In vivo somatostatin receptor-mediated scintigraphy has proven to be a valuable method for the visualisation of neuroendocrine tumours and their metastases. A new application is the use of radiolabelled analogues for somatostatin receptor-mediated therapy. This paper presents a review on the basic science, historical background and current knowledge of somatostatin receptor subtypes and their expression in neuroendocrine tumours. New somatostatin analogues, new chelators, "new" radionuclides and combinations thereof are also discussed. Due attention is given to limitations and future perspectives of somatostatin receptor-mediated imaging and therapy.     

Somatostatin receptor-mediated imaging and therapy: basic science, current knowledge, limitations and future perspectives

In vivo somatostatin receptor-mediated scintigraphy has proven to be a valuable method for the visualisation of neuroendocrine tumours and their metastases. A new application is the use of radiolabelled analogues for somatostatin receptor-mediated therapy. This paper presents a review on the basic science, historical background and current knowledge of somatostatin receptor subtypes and their expression in neuroendocrine tumours. New somatostatin analogues, new chelators, "new" radionuclides and combinations thereof are also discussed. Due attention is given to limitations and future perspectives of somatostatin receptor-mediated imaging and therapy.