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Immune-Neuro-Endocrine Reflexes, Circuits, and Networks: Physiologic and Evolutionary Implications. 免疫-神经-内分泌反射、回路和网络:生理和进化意义。
2区 医学 Q2 Medicine Pub Date : 2017-01-01 Epub Date: 2017-02-28 DOI: 10.1159/000452902
Adriana Del Rey, Hugo O Besedovsky

The existence of a network of interactions between the immune and nervous systems that influences host defenses and brain functions is now well-established. Here we discuss how immune and classical neuro/sensorial signals are processed in the brain and how neuro-endocrine immunoregulatory and behavioral responses are integrated. Considering the ability of brain cells to produce cytokines, originally described as immune cell products, we propose that the tripartite synapse plays a central role in the integration of neuro-endocrine-immune interactions. We also propose that the immune-neuro-endocrine responses that influence the course of transmissible and other diseases predisposing to infections can be relevant for evolution, either by restoring health or by mediating an active process of negative selection.

免疫系统和神经系统之间相互作用的网络影响宿主防御和大脑功能的存在现已得到证实。在这里,我们讨论了免疫和经典神经/感觉信号是如何在大脑中处理的,以及神经内分泌免疫调节和行为反应是如何整合的。考虑到脑细胞产生细胞因子的能力,最初被描述为免疫细胞产物,我们提出三方突触在神经-内分泌-免疫相互作用的整合中起着核心作用。我们还提出,影响传染性疾病和其他易感染疾病病程的免疫-神经-内分泌反应可能与进化有关,要么通过恢复健康,要么通过介导消极选择的积极过程。
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引用次数: 40
Intrahypophyseal Immune-Endocrine Interactions: Endocrine Integration of the Inflammatory Inputs. 垂体内免疫-内分泌的相互作用:炎症输入的内分泌整合。
2区 医学 Q2 Medicine Pub Date : 2017-01-01 Epub Date: 2017-02-28 DOI: 10.1159/000452904
U Renner, M Sapochnik, K Lucia, G K Stalla, E Arzt

Endotoxin (lipopolysaccharide, LPS) of gram-negative bacteria has been recognized for more than 40 years as a modulator of anterior pituitary hormone production. The action of LPS was thought to be predominantly mediated through LPS-stimulated immune cell-derived cytokines, and is part of the concept of immune-endocrine crosstalk, which regulates bidirectional adaptive processes between the endocrine and immune systems during inflammatory or infectious processes. With the detection of innate immune system components in the normal and tumoral pituitary, including the Toll-like receptor 4, the target of LPS, it has become evident that LPS can directly modify the physiology and pathophysiology of the anterior pituitary. LPS-induced intrapituitary mechanisms involve the stimulation of intrapituitary cytokines, and also directly act on hormone synthesis, growth, and apoptosis of endocrine cells. This review focuses on the effects of LPS on pituitary physiology, its interaction with pro- and anti-inflammatory factors, and the molecular mechanisms involved in these processes.

革兰氏阴性菌的内毒素(脂多糖,LPS)被认为是垂体前叶激素产生的调节剂已有40多年的历史。脂多糖的作用被认为主要是通过脂多糖刺激的免疫细胞源性细胞因子介导的,并且是免疫-内分泌串扰概念的一部分,在炎症或感染过程中调节内分泌和免疫系统之间的双向适应过程。随着在正常垂体和肿瘤垂体中检测到包括LPS靶点toll样受体4在内的先天免疫系统成分,LPS可以直接改变垂体前叶的生理和病理生理。lps诱导的垂体内机制包括对垂体内细胞因子的刺激,也直接作用于内分泌细胞的激素合成、生长和凋亡。本文就脂多糖对垂体生理的影响、与促炎因子和抗炎因子的相互作用以及参与这些过程的分子机制进行综述。
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引用次数: 5
Pituitary Autoimmunity. 垂体自身免疫。
2区 医学 Q2 Medicine Pub Date : 2017-01-01 Epub Date: 2017-02-28 DOI: 10.1159/000452905
Federica Guaraldi, Roberta Giordano, Silvia Grottoli, Lucia Ghizzoni, Emanuela Arvat, Ezio Ghigo

Pituitary autoimmunity, considered a synonym of autoimmune hypophysitis, defines a wide spectrum of conditions (neoplastic, functional, and iatrogenic pituitary disorders; and extra-pituitary autoimmune and non-autoimmune diseases), and is characterized by the presence of antipituitary antibodies (APAs) at various titer and prevalence. These conditions have been increasingly recognized not only in adults, but also in children. The autoimmune pathogenesis, histological features of the primary (i.e. lymphocytic, granulomatous, xanthomatous, IgG-4 related lymphoplasmacytic, and necrotizing) forms, and the pathognomonic association of lymphocytic hypophysitis with pregnancy and CTLA-4 antibody therapy, have been clearly demonstrated. Meanwhile, non-invasive differential diagnosis remains extremely challenging since none of the suggested clinical, radiological or laboratory criteria are pathognomonic. In this context, the demonstration of APA is not sufficient, because of the lack of specificity, and associated methodological and theoretical issues (i.e. disease marker vs. pathogen; antigen target(s); and diagnostic/prognostic significance). This chapter aims at providing a comprehensive overview of the pituitary autoimmunity panorama for epidemiological, clinical radiological, and histological aspects, while discussing the main diagnostic limitations and issues associated with disease management.

垂体自身免疫,被认为是自身免疫性垂体炎的同义词,定义了广泛的条件(肿瘤,功能性和医源性垂体疾病;以及垂体外自身免疫性和非自身免疫性疾病),其特征是存在不同滴度和患病率的抗垂体抗体(APAs)。越来越多的人认识到,这些情况不仅发生在成人身上,而且也发生在儿童身上。自身免疫发病机制、原发性(即淋巴细胞性、肉芽肿性、黄瘤性、IgG-4相关淋巴浆细胞性和坏死性)形式的组织学特征,以及淋巴细胞性垂体炎与妊娠和CTLA-4抗体治疗的病理关系,已被清楚地证明。与此同时,非侵入性鉴别诊断仍然极具挑战性,因为所建议的临床、放射学或实验室标准都不是典型的。在这种情况下,APA的证明是不够的,因为缺乏特异性,以及相关的方法和理论问题(即疾病标志物与病原体;抗原目标(s);以及诊断/预后意义)。本章旨在从流行病学、临床放射学和组织学方面全面概述垂体自身免疫全景,同时讨论与疾病管理相关的主要诊断局限性和问题。
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引用次数: 16
Leptin, Neuroinflammation and Obesity. 瘦素,神经炎症和肥胖。
2区 医学 Q2 Medicine Pub Date : 2017-01-01 Epub Date: 2017-02-28 DOI: 10.1159/000452908
Nathalia R V Dragano, Roberta Haddad-Tovolli, Licio A Velloso

Hypothalamic resistance to adipostatic actions of leptin is a hallmark of obesity. Studies have revealed that hypothalamic inflammation, triggered in response to the consumption of large amounts of dietary fat, is an important mechanism in the development of leptin resistance. In this chapter, we will review the work that paved the way linking neuroinflammation of the hypothalamus and defective leptin action in obesity.

下丘脑对瘦素的脂肪行为的抵抗是肥胖的一个标志。研究表明,由于摄入大量膳食脂肪而引发的下丘脑炎症是瘦素抵抗发展的重要机制。在本章中,我们将回顾为连接下丘脑神经炎症和肥胖中瘦素作用缺陷铺平道路的工作。
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引用次数: 27
Gonadal Imaging in Endocrine Disorders. 内分泌疾病的性腺成像。
2区 医学 Q2 Medicine Pub Date : 2016-03-21 DOI: 10.1159/000442319
F. Lanfranco, G. Motta
Ultrasound (US) is the most widely available method of diagnostic imaging for the evaluation and characterization of gonadal lesions and is usually the method of choice because of its high accuracy, low cost and wide availability. Today's high-resolution images allow for a confident diagnosis of many scrotal and adnexal lesions, with high sensitivity and specificity. Magnetic resonance imaging (MRI) is reliable in the detection of gonadal lesions in males, allowing the differentiation into testicular or nontesticular lesions, and their characterization. It is also an accurate and cost-effective diagnostic adjunct in those patients with solid scrotal lesions for whom the findings of clinical and US evaluations are inconclusive. In females, MRI is recommended as a second-line investigation for the characterization of complex adnexal masses that are indeterminate on US. In this review, gonadal pathologies related with the steroidogenic and gametogenic function of the testes and ovaries will be discussed. The main imaging features of benign and malignant lesions will also be presented.
超声(US)是最广泛使用的诊断成像方法,用于评估和表征性腺病变,通常是首选的方法,因为它的准确性高,成本低,可用性广。今天的高分辨率图像允许一个自信的诊断许多阴囊和附件病变,具有高灵敏度和特异性。磁共振成像(MRI)在男性性腺病变的检测中是可靠的,可以区分睾丸或非睾丸病变及其特征。对于那些临床和美国评估结果不确定的实心阴囊病变患者,它也是一种准确和经济有效的诊断辅助手段。在女性中,对于超声不确定的复杂附件肿块的特征,推荐MRI作为二线检查。本文将讨论与睾丸和卵巢的类固醇生成和配子体功能有关的性腺病理。良、恶性病变的主要影像学特征也将被介绍。
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引用次数: 1
Endoscopic Ultrasound in Endocrinology: Imaging of the Adrenals and the Endocrine Pancreas. 内窥镜超声在内分泌学:肾上腺和内分泌胰腺的成像。
2区 医学 Q2 Medicine Pub Date : 2016-03-21 DOI: 10.1159/000442277
P. Kann
Endoscopic ultrasound (EUS) imaging of adrenal glands and its application to diagnostic procedures of adrenal diseases has been reported since 1998. It can be considered a relevant advantage in the field of adrenal diseases. Indeed, EUS allows the detection of adrenal lesions (even very small ones) and their characterization, the assessment of malignancy criteria, the early detection of neoplastic recurrences, the preoperative identification of morphologically healthy parts of the glands, the differentiation of extra-adrenal from adrenal tumors, and of the pathological entities associated with adrenal insufficiency, and the fine-needle aspiration biopsy (EUS-FNA) of suspicious lesions. At the same time, its clinical relevance depends on the experience of the endosonographer. Moreover, EUS is also by far the best and most sensitive imaging technique to detect and assess the follow-up of pancreatic manifestation of MEN1 disease. It furthermore enables the preoperatively localization of insulinomas and critical structures in their neighborhood, and may be relevant in planning surgical strategy. A positive EUS in a case of insulinoma furthermore confirms the endocrine diagnosis, especially considering the differential diagnosis of hypoglycemia factitia by oral antidiabetics. It can be supplemented by EUS-FNA. Again, it has to be considered that EUS may reveal false positive and false negative results, and the quality of the findings largely depends on the endosonographer's skills and experience. The most important technical details together with the advantages and limitations of EUS, and the pathognomonic characteristic of benign and malignant disorders of the adrenals and pancreas are presented here.
自1998年以来,已报道了肾上腺的超声内镜成像及其在肾上腺疾病诊断中的应用。它可以被认为是肾上腺疾病领域的一个相关优势。事实上,EUS可以检测肾上腺病变(甚至是非常小的病变)及其特征,评估恶性肿瘤标准,早期发现肿瘤复发,术前识别腺体形态健康部位,区分肾上腺外肿瘤和肾上腺肿瘤,以及与肾上腺功能不全相关的病理实体,并对可疑病变进行细针穿刺活检(EUS- fna)。同时,其临床意义取决于超声医师的经验。此外,EUS也是迄今为止检测和评估MEN1疾病胰腺表现随访的最佳和最敏感的影像学技术。此外,它可以术前定位胰岛素瘤及其附近的关键结构,并可能与计划手术策略相关。1例胰岛素瘤EUS阳性进一步证实了内分泌诊断,特别是考虑到口服降糖药对原发性低血糖的鉴别诊断。它可以由eu - fna补充。再次,必须考虑到EUS可能会显示假阳性和假阴性结果,并且结果的质量在很大程度上取决于内镜医师的技能和经验。本文将介绍EUS最重要的技术细节、优点和局限性,以及肾上腺和胰腺良性和恶性疾病的病理特征。
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引用次数: 12
Role of Nuclear Medicine in the Diagnosis of Benign Thyroid Diseases. 核医学在良性甲状腺疾病诊断中的作用。
2区 医学 Q2 Medicine Pub Date : 2016-03-21 DOI: 10.1159/000442275
Sara Garberoglio, O. Testori
A deep understanding of thyroid pathophysiology is the basis for diagnosing and treating benign thyroid diseases with radioactive materials, known as radiopharmaceuticals, which are introduced into the body by injection or orally. After the radiotracer administration, the patient becomes the emitting source, and several devices have been studied to detect and capture these emissions (gamma or beta-negative) and transform them into photons, parametric images, numbers and molecular information. Thyroid scintigraphy is the only technique that allows the assessment of thyroid regional function and, therefore, the detection of areas of autonomously functioning thyroid nodules. Scintigraphy visualizes the distribution of active thyroid tissue and displays the differential accumulation of radionuclides in the investigated cells, thus providing a functional map. Moreover, this technique is a fundamental tool in the clinical and surgical management of thyroid diseases, including: single thyroid nodules with a suppressed thyroid-stimulating hormone level, for which fine-needle aspiration biopsy (FNAB) is used to identify hot nodules; multinodular goiters, especially larger ones, to identify cold or indeterminate areas requiring FNAB and hot areas that do not need cytologic evaluation, and to evaluate mediastinal extension; the diagnosis of ectopic thyroid tissue; subclinical hyperthyroidism to identify occult hyperfunctioning tissue; follicular lesions to identify a functioning cellular adenoma that could be benign, although such nodules are mostly cold on scintigraphy; to distinguish low-uptake from high-uptake thyrotoxicosis, and to determine eligibility for radioiodine therapy.
深入了解甲状腺病理生理是诊断和治疗良性甲状腺疾病的基础,放射性物质被称为放射性药物,通过注射或口服进入体内。在使用放射性示踪剂后,患者成为发射源,并且已经研究了几种设备来检测和捕获这些发射(γ或β负)并将其转换为光子,参数图像,数字和分子信息。甲状腺闪烁成像是唯一的技术,允许评估甲状腺区域功能,因此,检测自主功能甲状腺结节的区域。闪烁显像显示活跃甲状腺组织的分布,并显示放射性核素在被调查细胞中的差异积累,从而提供功能图。此外,该技术是甲状腺疾病的临床和外科治疗的基本工具,包括:单个甲状腺结节与抑制促甲状腺激素水平,其中细针穿刺活检(FNAB)用于识别热结节;多结节性甲状腺肿,特别是较大的甲状腺肿,以确定需要FNAB的寒冷或不确定区域和不需要细胞学评估的炎热区域,并评估纵隔延伸;异位甲状腺组织的诊断;亚临床甲状腺功能亢进识别隐匿功能亢进组织;滤泡性病变鉴别良性的功能性细胞腺瘤,尽管这种结节在显像上大多是冷的;目的:区分低摄取和高摄取甲状腺毒症,并确定是否适合放射性碘治疗。
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引用次数: 12
Molecular Imaging of Pituitary Pathology. 垂体病理分子成像。
2区 医学 Q2 Medicine Pub Date : 2016-03-15 DOI: 10.1159/000442329
Wouter W de Herder
The presence of large numbers and/or the high affinity of dopamine D2 and/or somatostatin receptors on pituitary adenomas may enable their visualization with radionuclide-coupled receptor agonists or antagonists. However, the role of these imaging modalities in the differential diagnosis of or therapeutic purposes for pituitary lesions is very limited. Only in very specific cases might these molecular imaging techniques become helpful. These include the differential diagnosis of pituitary lesions, ectopic production of pituitary hormones, such as adrenocorticotrophic hormone, growth hormone (GH) or their releasing hormones (corticotropin-releasing hormone and GH-releasing hormone), and the localization of metastases from pituitary carcinomas.
多巴胺D2和/或生长抑素受体在垂体腺瘤上大量和/或高亲和力的存在,可能使放射性核素偶联受体激动剂或拮抗剂能够显示它们。然而,这些成像方式在垂体病变的鉴别诊断或治疗目的中的作用非常有限。只有在非常特殊的情况下,这些分子成像技术才会有用。这些包括垂体病变的鉴别诊断,垂体激素的异位分泌,如促肾上腺皮质激素、生长激素(GH)或其释放激素(促肾上腺皮质激素释放激素和GH释放激素),以及垂体癌转移灶的定位。
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引用次数: 2
Hybrid Molecular Imaging in Differentiated Thyroid Carcinoma. 分化型甲状腺癌的杂交分子显像。
2区 医学 Q2 Medicine Pub Date : 2016-03-15 DOI: 10.1159/000442276
D. Schmidt, T. Kuwert
Radioactive isotopes of radioiodine are frequently used in differentiated thyroid carcinoma (DTC) both for diagnosis and therapy. Their accumulation in thyroid cancer tissue is dependent on the expression and activity of the sodium-iodide symporter (NIS). Scintigraphic imaging using either planar or single-photon emission computed tomography (SPECT) cameras allows the visualization of their distribution within the human body. Due to only a poor visualization of morphology by these techniques, their diagnostic accuracy is, however, limited. This limitation is overcome when hybrid systems integrating a SPECT camera with an X-ray CT scanner are used. Roughly one third of patients with diagnostically unclear foci of radioiodine accumulation will benefit from the use of SPECT/CT, also in terms of therapeutic management. SPECT/CT has, therefore, become the gold standard of nuclear imaging in DTC. NIS expression may be absent in DTC. In this case, the glucose transporters are usually upregulated. Therefore, PET/CT using 18F-deoxyglucose can be used to diagnose and localize tumor recurrence as a prerequisite to, in particular, surgical intervention.
放射性碘的放射性同位素常用于分化型甲状腺癌(DTC)的诊断和治疗。它们在甲状腺癌组织中的积累依赖于碘化钠同调体(NIS)的表达和活性。使用平面或单光子发射计算机断层扫描(SPECT)相机的闪烁成像可以可视化它们在人体内的分布。然而,由于这些技术的形态学可视化效果很差,其诊断准确性受到限制。当使用集成SPECT相机和x射线CT扫描仪的混合系统时,可以克服这一限制。大约三分之一的放射性碘积聚灶诊断不明确的患者将受益于SPECT/CT的使用,也在治疗管理方面。因此,SPECT/CT已成为DTC核成像的金标准。DTC中可能没有NIS的表达。在这种情况下,葡萄糖转运蛋白通常被上调。因此,使用18f -脱氧葡萄糖的PET/CT可作为诊断和定位肿瘤复发的先决条件,特别是手术干预。
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引用次数: 3
Adrenal Molecular Imaging. 肾上腺分子成像。
2区 医学 Q2 Medicine Pub Date : 2016-03-15 DOI: 10.1159/000442317
A. Sundin
The major workload in the field of adrenal imaging comprises patients with adrenal tumors incidentally depicted by imaging performed for other reasons than adrenal disease. These so-called 'incidentalomas' are generally managed by CT and MRI, and molecular imaging techniques are required only for a few patients. PET/CT with 18F-fluorodeoxyglucose (18F-FDG) is useful for establishing whether an adrenal metastasis is the only lesion, and therefore is available for surgical resection, or if the disease is disseminated. 18F-FDG PET/CT may be applied to differ benign from malignant incidentalomas and can be helpful in the imaging of pheochromocytoma and adrenocortical cancer (ACC). 11C-metomidate PET/CT can differentiate adrenocortical from nonadrenocortical tumors and a suspected ACC may be characterized and staged before surgery. 11C-metomidate PET/CT is currently also used to help diagnose Conn's adenomas in primary aldosteronism, but further development is needed. Scintigraphy with 123I/131I-metaiodobenzylguanidine (MIBG) remains the mainstay for molecular imaging of pheochromocytoma and is mandatory in patients for whom 131I-MIBG therapy is considered. A PET tracer for the imaging of pheochromocytoma is the norepinephrine analogue (11)C-hydroxyephedrine that can be used to characterize equivocal lesions and for the follow-up and diagnosis of recurrent malignant disease. Other specialized PET tracers for the imaging of pheochromocytoma are 18F-fluorodihydroxyphenylalanine (18F-DOPA) and 18F-fluorodopamine.
肾上腺成像领域的主要工作量包括因肾上腺疾病以外的其他原因进行成像偶然描述的肾上腺肿瘤患者。这些所谓的“偶发瘤”通常通过CT和MRI进行治疗,只有少数患者需要分子成像技术。PET/CT与18f -氟脱氧葡萄糖(18F-FDG)有助于确定肾上腺转移是否是唯一的病变,因此可用于手术切除,或者如果疾病弥散。18F-FDG PET/CT可用于区分良性和恶性偶发瘤,并有助于嗜铬细胞瘤和肾上腺皮质癌(ACC)的成像。11C-metomidate PET/CT可区分肾上腺皮质与非肾上腺皮质肿瘤,疑似ACC可在术前进行特征和分期。11c -甲咪酯PET/CT目前也用于帮助诊断原发性醛固酮增多症的Conn腺瘤,但需要进一步发展。123I/131I-metaiodobenzylguanidine (MIBG)闪烁成像仍然是嗜铬细胞瘤分子成像的主要方法,对于考虑使用131I-MIBG治疗的患者是强制性的。一种用于嗜铬细胞瘤成像的PET示踪剂是去甲肾上腺素类似物(11)c -羟麻黄碱,可用于表征模棱两可的病变,并用于复发性恶性疾病的随访和诊断。其他用于嗜铬细胞瘤成像的专用PET示踪剂有18f -氟二羟基苯丙氨酸(18F-DOPA)和18f -氟多巴胺。
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引用次数: 5
期刊
Frontiers of Hormone Research
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