Characterization of two distinct mechanisms for induction of apoptosis in human vascular endothelial cells.

Tissue homeostasis is fundamentally influenced by the functional integrity and state of endothelial cells. Survival and death of endothelial cells are encountered in cardiovascular disease and may, moreover, affect and determine the development of atherosclerosis and restenosis following intracoronary therapeutical interventions. Apoptosis was studied in cultured human umbilical vein endothelial cells (HUVEC) to investigate the regulation of endothelial cell death following serum/growth factor depletion as well as incubation with actinomycin-D. Apoptosis was verified by DNA fragmentation and quantified by fluorescence activated cell sorting (FACS) analysis after TdT-mediated deoxyuridine-triphosphate nick end-labeling (TUNEL). An ELISA was used for detecting intracytoplasmatic nucleosomes. Untreated HUVEC showed 16+/-6% TUNEL positive cells after 24 hours as analyzed by FACS. Serum/growth factor depletion increased apoptosis by 79+/-7%, while 50 ng/ml of the pro-apoptotic drug actinomycin-D induced comparable effects (72+/-11%). Apoptosis by serum/ growth factor depletion could be blocked completely by the anti-apoptotic agent cycloheximide (2 microg/ml), but was ineffective in blocking actinomycin-D-induced apoptosis. Pyrrolidine dithiocarbamate (PDTC) also acted as an anti-apoptotic agent by blocking apoptosis induced by actinomycin-D, but had no effect on apoptosis induced by factor depletion. Thus, two independent mechanisms for regulation of apoptosis are suggested to be present in human vascular endothelial cells.

Clinical and experimental investigations of vasopressin secretion in acute porphyrias.

In 41 patients suffering from acute hepatic porphyrias the arginin-vasopressin (AVP) levels in their urine were measured by RIA. In 6 patients, AVP secretion was normal; in 8 cases AVP levels were significantly elevated, while 27 cases showed decreased levels of AVP (p less than 0.001). A linear correlation between AVP secretion and urine volume was not found. In animal experiments, 20 rats were treated with delta-aminolevulinic acid (ALA), (1.5 mmol/kg/24 h and 1.5 mmol/kg/48 h) for 4 weeks. Afterwards vasopressin production in the hypothalamo-hypophyseal system was analysed by the immunoperoxidase technique and a microdensitometric method. In ALA-treated animals, AVP positive neurones showed coarse-grained granules of different intensity and a distinct increase of peroxidase positive granules in the zona interna of the eminentia mediana. Furthermore, in comparison with the control group in ALA-treated animals the mean diameter of nuclei in AVP positive neurons was greater. While animals treated daily showed an increase of transmission in the pituitary, microdensitometric findings in animals treated at 48 hourly intervals showed an equal transmission in AVP producing nuclei compared to the control group. Our results seem to point to a toxic effect of porphyrin precursors on the CNS, which may also induce via hypothalamus lesion either diabetes insipidus or a SIADH-syndrome.

Headaches after childbirth.

71 women were examined daily for the presence of headache in their first post partum week. Post natal headache (PNH) occurred in 27, (39%) of the women and was most frequent on days 4-6 post partum. PNH was significantly associated with a previous or family history of migraine and pre-menstrual migraine. Although 83% of those with PNH had a migraine diathesis, they did not describe their headache as one of their usual migraines as it was considerably milder. Headaches were more frequent among multigravida but as rather more multigravida had a previous migraine diathesis this may reflect a sampling bias. PNH subjects had significantly more tension and depression suggesting that at least some PNH may be tension headache. Around 3 or 4 days post partum, women began to lose weight and the onset of headache often coincided with the start of this weight loss. 12 women with, and 12 without PNH took part in a metabolic study, and collected sequential 24 h urine samples from days 2-7 post partum. Potassium and oestrogen excretion were increased on day 3, and progesterone on days 3, 4 and 5. Differences in the excretion pattern of these hormones might reflect small changes in renal function and further work measuring plasma hormone levels could help to clarify this. PNH, like pre-menstrual headache and pill withdrawal headache may represent a further example of the triggering effect that a fall in sex hormone level has on the migraine diathesis.

[Immunohistochemical demonstration of arginin-vasopressin in the diencephalon of rats with experimental hydrocephalus internus]. / Immunhistochemischer Nachweis von Arginin-Vasopressin im Diencephalon der Ratte mit experimentellem Hydrocephalus Internus.

The synthesis of vasopressin in hydrocephalic rats has been studied by immunohistochemical, karyometrical and densitometrical methods. Signs of a decreased synthesis of vasopressin in the hypothalamo-neurohypophyseal system were found. No signs of a diabetes insipidus were observed.

[Anabolic therapy in metastatic breast cancer]. / Anabole Therapie bei metastasierendem Mamma-Karzinom.

The medical records of 66 women treated with metenolone for metastasized breast carcinomas were analysed. In 26 patients a remission developed with a mean duration of 8.2 (3-29) months. Patients whose treatment started in the first year after the menopause as well as patients with a beneficial effect of a therapeutic ovariectomy in the past were more often improved by metenolone than average. Metenolone had a better effect against osseous metastases than against visceral metastases. In most cases the treatment was well tolerated. In four patients, however, the treatment had to be interrupted because of cholestasis, pulmonary embolism and hypercalcaemia.

The rhombencephalic recess in the rat. A light and electron microscopic study.

The rhombencephalic recess, an ependymal organ, has been studied for the first time by light- and electron microscopy. It is situated mediosagitally on the floor of the rhomboid fossa at the level of the colliculus facialis. The recess and the superimposed tissue are built up by tanycytes, their apices being connected by tight junctions. HRP, injected into the c.s.f., does not penetrate into the intercellular clefts of the recess area. The recess area reveals a certain autonomy regarding its supply with arteries and capillaries. A blood-brain barrier exists, but shows slight leakage in circumscribed areas as a result of intense transendothelial vesicular transport. The organization of the recess area is compared with that of other ependymal organs, especially circumventricular organs.

[Connective tissue in the perivascular spaces of subependymal capillaries of the spinal cord in the rabbit]. / Bindegewebe in perivaskulären Räumen subependymaler Kapillaren des Rückenmarkes beim Kaninchen.

The normal structure of the subependymal capillaries and venules of the spinal cord was studied in rabbit. The endothelial cells of the capillaries and venules are surrounded by an irregularly formed perivascular space, about 0.5 to 3.3 micrometer wide, which is delimited by an endothelial and glial basal lamina. The space contains a framework of collagen fibers. A period-acid-bisulfit-aldehydthionine-method (Specht) permits to find the perivascular connective tissue lightmicroscopically, while they can be identified by electron microscopy. The significance of the perivascular connective tissue is open to discussion. Structural and functional problems have been reviewed in this context.

Recent observations on ependyma and subependymal basement membranes.

Directly under the ependyma, and between the ependymal cells, there are basement membranes which form labyrinths connecting with the perivascular basement membranes of the subependymal vessels. The basement membranes exhibit differences in form, position, and distribution, and they can be distended by fluid absorption into large lacunae. The membranes can be identified as glycoprotein and glylcolipid substances. Electron microscopic studies have shown the differences between the basement membrane labyrinths of the human, the rabbit and the rat. In the human, the labyrinths contain isolated collagen fibrils. Basement membranes generally line all connective tissue spaces and form their interstitial borders. From this point of view, the subependymal basement membrane labyrinths can be seen as interstitial spaces near the ventricles, forming pathways between the ependyma and the subependymal capillaries or postcapillary veins.