Inhibitory effects of fumagillin and its analogue TNP-470 on the function, morphology and angiogenesis of an oestrogen-induced prolactinoma in Fischer 344 rats.

The process of angiogenesis occurs in many physiological states, but it is also essential for the growth of solid tumours and metastasis formation. An abnormal arterial vascularization has been shown in prolactin-secreting pituitary adenomas induced by prolonged treatment with oestrogens in Fischer 344 (F344) rats. It is thought that anti-angiogenic agents might be useful in therapy for these tumours. Fumagillin and its analogue TNP-470 are known to inhibit endothelial cell proliferation selectively, but their effect on lactotroph cell secretory function and prolactinoma formation has not yet been described. The aim of the present study was to examine the effects of fumagillin and TNP-470 on prolactin secretion, and morphological and vascular changes within the anterior pituitary in long-term oestrogen-treated male F344 rats in vivo and in vitro. As expected, 7 weeks after s.c. implantation of Silastic tubes containing 10 mg diethyl-stilboestrol (DES), a very high rise in serum prolactin levels was found. Both angiogenesis inhibitors injected s.c. at doses of 10 mg/kg body weight for 24 days attenuated the stimulatory effect of DES on prolactin production and release. They also diminished prolactin cell density and inhibited cell proliferation expressed as the number of anterior pituitary cells labelled with bromodeoxyuridine (BrdU), but the effect of TNP-470 was minor compared with fumagillin. Both angioinhibitors suppressed neo-vascularization within the anterior pituitary with similar potency but, on the other hand, they did not affect DES-induced increases in prolactin secretion from cultured rat pituitary cells and cell proliferation in vitro. In conclusion, our results provide strong evidence for the anti-tumour and anti-prolactin activity of angiogenesis inhibitors in the experimentally oestrogen-induced pituitary adenoma; this might be mediated indirectly through the inhibition of angiogenesis.

[Results of treatment of giant cerebral aneurysm in patients at the Department Neurosurgery, Academy of Medicine, in Lodz]. / Wyniki leczenia tetniaków olbrzymich mózgu w materiale Kliniki Neurochirurgii AM w Lodzi.

The authors discuss the results of surgical treatment of 45 patients with giant intracranial aneurysms calling attention to more frequent occurrence of subarachnoid haemorrhage as the presenting signs, and to the most effective treatment method that is closing of aneurysm neck with a clip, especially in aneurysms of the internal carotid artery. Ligation of aneurysm neck, non-radical operations, other location of the aneurysm, serious condition of the patient and repeated subarachnoid haemorrhages worsen the therapeutic results.

Effect of amantadine on prolactin secretion, pituitary DNA synthesis and 3H-spiperone binding in male estrogen-treated rats.

Amantadine, a well-known antiviral agent, causing an increase in dopamine synthesis, release and the inhibition of re-uptake of noradrenaline and dopamine in central and peripheral catecholaminergic neurons, is successfully used in the treatment of Parkinson's disease. In the present paper, we have studied the effect of various doses of amantadine on in vivo prolactin secretion and the incorporation of 3H-thymidine and 3H-spiperone binding by the anterior pituitary gland of long-term diethylstilboestrol-treated male Wistar rats. Four weeks after a subcutaneous implantation of Silastic tubes containing 10 mg of diethylstilboestrol, a dramatic rise in serum prolactin levels was observed, accompanied by an increased uptake of 3H-thymidine by DNA anterior pituitary cells. Amantadine, given in the subcutaneous doses of 50, 5 and 0.5 mg/kg of body weight attenuated the stimulatory effect of stilboestrol on serum prolactin concentration in a dose-dependent fashion. On the other hand, the incorporation of 3H-thymidine into DNA pituitary cells in all the groups of amantadine-treated rats was only slightly suppressed. In an additional experiment, Scatchard analyses were performed on the in vitro 3H-spiperone binding kinetics in a dispersed anterior pituitary cell culture prepared from the pituitaries of 6-week diethylstilboestrol-treated rats. It has been found that amantadine injected in the dose of 5 mg/kg of body weight for 14 days induced a twofold decrease in the density of dopamine D2 binding sites (36.6 +/- 9.4 vs. 70.3 +/- 3.4 fmol/10(6) cells; p less than 0.02), while the apparent affinity of the receptors was unchanged.(ABSTRACT TRUNCATED AT 250 WORDS)

Changes of blood flow in the adenohypophysis of normal and estrogen pretreated Fisher rats by tamoxifen.

Blood flow was measured in the adenohypophysis and in the cerebral cortex of female F344 rats over a period of 90 min using the hydrogen clearance method. Tamoxifen, 1 mg/kg, administered iv reduced the blood flow in the adenohypophysis by 35%, whereas cerebral blood flow and arterial pressure remained unchanged. Seven days sc treatment with tamoxifen (1 mg/kg daily) had no demonstrable effect on blood flow. Anterior pituitary hyperplasia was induced in 15 rats with diethylstilbestrol containing implants. These rats responded to 7 days of sc tamoxifen treatment by 30% increase in adenohypophyseal blood flow. These results suggest that tamoxifen has a different effect on adenohypophysial circulation of the rat depending on whether it is administered in a low- or high-estrogen state.

Spinal chronic subdural haematoma in a 7-year old girl.

A case is reported of chronic encapsulated spinal subdural haematoma which developed in a 7-year-old girl after minor spinal trauma. Surgical removal of the lesion was followed by complete recovery.

Changes of blood flow in oestrogen-induced hyperplastic anterior pituitary lobe following bromocriptine administration.

Anterior pituitary hyperplasia and histologically verified adenomas were induced by diethylstilboestrol (DES) containing implants in a total of 104 female F344 rats. Thirty rats were used as controls. Blood flow in the anterior pituitary (PBF) was measured using the hydrogen clearance method. PBF was progressively reduced to 25% by DES in 13 weeks but the total adenohypophysial blood flow (flow as measured per unit weight multiplied by weight of the gland) was raised by 75%. Bromocriptine (BC, 1 mg/kg intravenously) reduced PBF by a maximum of 27% in tumour-bearing rats. When bromocriptine (1 mg/kg/day subcutaneously) was given for 7 days before the measurements the hyperplastic effect of DES on the pituitary gland and the total blood flow through the pituitary were both reduced by 23%. Reduction of blood supply may be one of the reasons that bromocriptine is clinically useful.

Blood flow in diethylstilbestrol-induced anterior pituitary gland hyperplasia.

Anterior pituitary hyperplasia was developed in female Fisher 344 rats by subcutaneously implanted slow-release diethylstilbestrol (DES) capsules. Blood flow was measured in two separate areas of the adenohypophysis using hydrogen clearance method at 6, 9, 10, and 13 weeks after the implantation. Blood flow progressively decreased while the DES capsules were in place (normal values in ml/g/min, mean +/- SD: 0.93 +/- .12 laterally and 1.15 +/- .11 medially, decreasing to 0.25 +/- .07 and 0.24 +/- .07, respectively, by 13 weeks). Histology confirmed nodular hyperplasia, development of large vascular lakes, and hemorrhages within the adenohypophysis. Total adenohypophysial blood flow was calculated as a product of mean blood flow as measured per unit weight and the weight of the gland. This figure progressively increased from 12.7 +/- 2 to 22.2 +/- 8 microliter/min by 13 weeks. All these changes were significant at the P less than 0.001 level. These blood flow measurements suggest that the hyperplastic adenohypophysis outgrows its blood supply which is additionally compromised by "useless" pooling of blood in the vascular lakes. However, there is an overall increase in the amount of blood flowing through the hyperplastic gland which may be explained by newly formed supplying vessels.

Increased CSF levels of somatostatin in patients with brain tumours and intracranial hypertension.

The cerebrospinal fluid (CSF) levels of somatostatin in patients with brain tumours, communicating hydrocephalus, lumbar-disc disease (treated as a control) were measured by specific radioimmunoassay. The somatostatin concentration in the patients with brain tumours and intracranial hypertension was significantly higher compared to those with brain tumours and normal CSF pressure. CSF somatostatin content in patients with communicating hydrocephalus, was similar to patients with brain tumours and normal CSF pressure, and did not show a significant difference from the control group. The authors discuss possible reasons for such results obtained in patients with brain tumours and intracranial hypertension.

[Clinico-radiological picture of periradicular cysts in the lumbosacral region]. / Obraz kliniczno-radiologiczny torbieli okolokorzeniowych w odcinku ledzwiowo-krzyzowym.

After a review of the modern views on the problem of the so called Tarlov's cysts the authors present a group of 20 patients with chronic low back pains in whom periradicular cysts were diagnosed demonstrating them by means of Dimer-X radiculography. In the light of an analysis of this material the authors reach the conclusion that there are no specific symptoms and signs which could make possible the diagnosis of Tarlov's cysts without contrast radiography of the dural sac. There are, moreover, no reliable data demonstrating that the clinical manifestations in patients with Tarlov's cysts are indeed caused by them since surgical verification demonstrates often other causes of pain.