Endogene Natriuretische und Ouabain-ähnliche Faktoren

Summary The existence of an endogenous natriuretic hormone and ouabain-like factors (OLF) has been postulated for many years. This postulate was based on our original observation that a small M.W. fraction in the serum after acute expansion of the extracellular fluid volume (ECFV) not only exhibited natriuretic activity but also inhibited the Na-K-ATPase enzyme in vitro similar to ouabain. Since then, numerous studies confirmed the presence of OLFs in serum, urine, cerebrospinal fluid, and various organs including the heart and hypothalamus. Some of these OLFs are well-known endogenous compounds, such as free unsaturated fatty acids, which inhibit in vitro transmembranous sodium transport, Na-K-ATPase and³H-ouabain binding to its membrane receptor or crossreact with digoxin antibodies. Chemically yet undefined OLFs of potentially hypothalamic origin were detected in various models of experimental and clinical hypertension and are suggested to play a pathophysiological role especially in salt- and volume-dependent forms of hypertension. Our results show that OLFs isolated from the urine of salt-loaded healthy subjects strongly enhance basal and vasopressin-stimulated release of calcium in vascular smooth muscle cells and platelets similar to the effects we had observed with endothelin. This urine fraction also exhibits natriuretic activity which increases in parallel with sodium intake. Further chromatographic separation and amino acid analysis confirmed the peptidic nature (M.W.<1000) of the natriuretic factor(s). However, the two biological activities, namely natriuretic and ouabain-like activities, reside in distinct and chemically different compounds. In face of the previous discovery of the atrial natriuretic peptides (ANP) it is of special interest that very recent observations strongly suggest a natriuretic factor of non-cardiac origin to play an important role in the natriuresis that follows ECFV expansion. In addition, numerous experimental data point to an interaction between the ANP and OLF systems. They should stimulate once again the final identification of these yet unknown endogenous natriuretic and ouabain-like factors.

Die in dieser übersicht zitierten eigenen Untersuchungen wurden von der Deutschen Forschungsgemeinschaft, Bonn, dem Ministerium für Wissenschaft und Forschung des Landes Nordrhein-Westfalen (FA-2914, FA-8871, IVA6-402-046-87), Düsseldorf, und der Konrad-Adenauer-Stiftung, Bonn, unterstützt     

ANF-Konzentrationen und Drücke im kleinen Kreislauf unter Belastung vor und nach Koronardilatation

Summary According to several reports of close correlations between pulmonary artery pressure and ANF plasma levels it would be convenient to replace invasive pressure monitoring by ANF determination.Mean pulmonary artery and right atrial pressures and pulmonary artery as well as peripheral venous ANF plasma concentrations were measured in 24 patients before and after coronary angioplasty (PTCA) continuously at rest and during exercise: At rest, both pressure and ANF-values remained unchanged before and after PTCA. At exercise, there was a decrease of mean pulmonary artery pressure (from 41.3±8.6 to 31.5±7.4 mmHg,p<0.001), mean right atrial pressure (from 11.9±3.0 to 9.0±2.3 mmHg,p< 0.001), pulmonary artery (282.5±191.0 to 207.3±157.2 pg/ml,p<0.05) and peripheral venous (112.7±48.0 to 97.1±53.2 pg/ml, n.s.) ANF concentration after PTCA. We found no correlation between PTCA-induced changes of right arterial pressures and ANF concentrations, while changes of pulmonary artery pressures were significantly correlated to changes of peripheral venous (r=0.79,p<0.001) as well as pulmonary artery (r=0.59,p<0.01) ANF concentrations at exercise. In 6 of the 24 patients, however there was an inverse relationship between changes of pulmonary artery pressures and ANF concentrations. — Our data demonstrate a significant correlation between changes of ANF plasma level and pulmonary artery pressure values at exercise after PTCA. In the individual case however invasive pressure monitoring cannot be replaced by determination of ANF plasma levels.

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Abkürzungsverzeichnis ANF Atrialer natriuretischer Faktor - PTCA Perkutane transluminale Koronarangioplastie - PPa mittlerer pulmonalarterieller Druck - PPc mittlerer pulmonalcapillärer Druck - PRA mittlerer rechtsatrialer Druck Herrn Prof. Dr. med F. Scheler zum 65. Geburtstag gewidmet     

Hypercalcemia in breast cancer

Hypercalcemia is relatively frequent in malignancy with or without osteolytic bone metastases. It is thought that neoplastic cells may secrete substances which not only stimulate osteoclastic activity but are also capable of modifying the absorption, excretion, and resorption of calcium and phosphate ions. Since 1987, we have studied 24 breast cancer patients with hypercalcemia (22 with bone metastases and two without). The group of 22 patients with bone metastases were divided into two subgroups. The first consisted of 10 patients with high serum levels of humoral factors, such as parathyroid hormone-related protein (PTHrP), and/or prostaglandin E₂ (PGE₂) and/or interleukin 1 (IL-1), and high levels of bone markers, such as alkaline phosphatase, bone Gla protein and urinary hydroxyproline. The second subgroup consisted of 12 patients with high levels of bone markers alone. Bone histologic analysis showed an osteoclastic activation surrounding metastatic tumor tissue in six out of 10 patients of the first subgroup, while an evident osteolysis caused by the tumor cells was noted in seven out of 12 patients of the second subgroup. The two patients without bone metastases showed normal biochemistry and bone histologic examination. The authors, having tried to explain the pathogenesis of hypercalcemia, emphasize the importance of humoral factors secreted by tumor cells as a direct or indirect cause of hypercalcemia. The origin of hypercalcemia remains unclear in two patients without bone metastases.     

Electron Microscopic Study of Adenoid Cystic Carcinoma

This ultrastructural study is based on nine cases of adenoid cystic carcinoma arising from the salivary glands. Electron microscopically, the tumors consisted of five cell types: relatively differentiated intercalated duct cells, secretory cells, undifferentiated cells, cells of a squamous nature, and myoepithelial cells. Special attention was paid to the characteristic extracellular substances noted by light microscopic examination of these tumors. The hyaline material of the pseudocysts contained not only mucopolysaccharide granules but also fingerprintlike structures formed by replicated basement membrane. Some of these structures had a dense core, probably composed of mucopolysaccharide granules. Cell islands surrounded by elasticlike material also were found. The true lumina were usually filled with membranovesicular structures originating from fragments of the lining cells, mainly those with squamous differentiation. These membranovesicular structures included electron-dense rods, filamentous whorls, and structures displaying periodicity.     

Intracerebroventricularly administered corticotropin-releasing factor releases somatostatin through a cholinergic,vagal pathway in freely fed rats

The aim of this study was to investigate whether corticotropin-releasing factor influences the plasma levels of somatostatin, gastrin or cholecystokinin when administered intracerebroventricularly to rats, and if such an effect could be vagally mediated, and dependent on the animals feeding states. Anaesthetized, freely fed rats were given 5 μl intracerebroventricular injections of corticotropin-releasing factor in four doses; 10 pmol-1.28 nmol. Immediately following death, trunk blood was collected for subsequent peptide analysis with radioimmunoassay (RIA). The three higher doses of corticotropin-releasing factor elevated the plasma levels of somatostatin (P < 0.01) after 20 min but left the plasma levels of gastrin and cholecystokinin unchanged. Intraperitoneal injections of 60 and 320 pmol of corticotropin-releasing factor did not influence the somatostatin levels. Further, intracerebroventricular injections of 60 pmol of corticotropin-releasing factor produced a peak increase in somatostatin after 20 min (P < 0.01). After 60 min the somatostatin levels were still increased (P < 0.05). Gastrin and cholecystokinin remained unaltered at these timepoints. Intracerebroventricular administration of 10 nmol of a-helical corticotropin-releasing factor 9–41 attenuated the basal levels of somatostatin and blocked the corticotropin-releasing factor-induced rise in somatostatin. Bilateral truncal vagotomy, as well as pretreatment with atropine (0.05 mg kg^-1, subcutaneously) abolished the effects of corticotropin-releasing factor on somatostatin. In animals which were food-deprived for 24 h, corticotropin-releasing factor did not influence somatostatin, gastrin or cholecystokinin. Pretreatment with cholecystokinin did not potentiate corticotropin-releasing factor-induced somatostatin release in food-deprived rats. These findings suggest that corticotropin-releasing factor acting within the central nervous system may regulate gastrointestinal functions partially through a cholinergic, vagally mediated release of somatostatin in freely fed, but not in food-deprived rats.     

An ultrastructural and immunohistochemical study of microcystic meningioma with emphasis on matrix proteins and connexin 26 type gap junctions

Although the histopathological subtypes of meningioma do not themselves appear to have prognostic significance, they are collectively important for defining the overall histopathological entity of microcystic meningioma (MCM) and allowing a distinction from other intracranial tumors, such as capillary hemangioblastoma, glioma, and metastatic renal cell carcinoma showing similar histology. Four cases of MCM were analyzed by conventional histology, immunohistochemistry, and electron microscopy. The present series of MCM was characterized by spindle- or cobweb-shaped tumor cells, characteristically associated small blood vessels, and a peculiar microcystic pattern. Among the microcystic meningeal tumor tissue, small areas of conventional subtypes were identified. Immunohistochemically, tumor cells showed the mesenchymal features of vimentin positivity and a rich distribution of matrix proteins around tumor cells. They lacked epithelial marker positivity but were faintly EMA positive. Ultrastructurally, primitive cellular junctions, desmosomes, and gap junctions were frequently seen between tumor cells. The gap junctions correlated with connexin 26 immunoreactivity. Although lacking an obvious epithelial nature, these features could be interpreted as showing an abortive differentiation mimicking meningothelial (arachnoidal) cells, which, physiologically, regulate cerebrospinal fluid between blood vessels and brain parenchyma.     

脑肿瘤患者认知功能障碍的初步研究

目的 :探索脑肿瘤患者认知功能障碍的特点。方法 :采用CLB测验对 31例左侧大脑肿瘤患者、34例右侧大脑肿瘤患者及正常对照组进行测验。结果 :(1)左侧大脑脑肿瘤组四项语言—序贯能力测验成绩明显低于对照组 (P <0 .0 5 ) ,四项空间认知能力成绩无明显差别 (P >0 .0 5 ) ,病例组CLQ为正值 ,表明右半球信息加工能力无明显损害 ;(2 )右侧大脑脑肿瘤组四项空间认知能力测验成绩明显低于对照组 (P <0 .0 5 ) ,四项语言—序贯能力测验成绩中系列数字、偏旁组字、类别组词与对照组间无明显差异 (P >0 .0 5 ) ,系列声音测验成绩有明显差异 (P <0 .0 5 ) ,病例组CLQ为负值 ,表明左半球信息加工能力基本正常。结论 :CLB可以对脑肿瘤患者认知功能障碍进行量化 ,是一种评估左右侧大脑肿瘤患者认知功能障碍的有效方法。     

P>胰岛素样生长因子-1抑制β淀粉样蛋白25～35诱导的神经干细胞凋亡/P>

目的 观察β-淀粉样蛋白(Aβ)对神经干细胞(NSCs)增殖和凋亡的影响,探讨胰岛素样生长因子-1(IGF-1)对Aβ介导的NSCs毒性作用的保护机制.方法 从E14 SD大鼠大脑中分离神经干细胞,分别用Aβ、IGF-1和Aβ加IGF-1处理,锥虫蓝(trypan blue)染色确定细胞死亡数量和细胞死亡率,BrdU标记并分析细胞增殖能力,免疫细胞化学法鉴定神经干细胞和新生细胞,TUNEL技术检测凋亡细胞.结果 IGF-1处理时细胞死亡率低下,有大量BrdU阳性细胞生成,但无TUNEL阳性细胞.Aβ处理组细胞死亡率在6～48 h快速上升,并形成大量TUNEL阳性细胞.而IGF-1加Aβ处理时,细胞死亡率较Aβ组显著下降.TUNEL阳性细胞显著减少.结论 Aβ促进神经干细胞死亡和凋亡;而IGF-1促进神经干细胞增殖并抑制由Aβ诱导的神经干细胞凋亡.