SUMMARY A case is presented in which a histologically proven prolactin secreting pituitary macroadenoma was associated with a large suprasellar craniopharyngioma. The pre-operative prolactin concentration was 8180mU/l. Although hyperprolactinaemia up to 3000mU/l in patients with a craniopharyngioma is usually due to stalk compression, greater values may indicate an associated prolactinoma.Craniopharyngioma may be associated with moderate hyperprolactinaemia, galactorrhoea and disturbance of the hypothalamo-pituitary-gonadal axis.' 4 However, in these cases as serum prolactin concentrations are usually less than 3000 mU/l (150ng/ml) and histo-pathological studies do not show prolactin secreting adenomata, the elevated levels are probably due to stalk compression.5 We report the first case in which a large suprasellar craniopharyngioma was associated with a prolactin secreting pituitary adenoma. Case reportA 61-year-old man presented with a 9 month history of gradually deteriorating vision and difficulty with lateral vision while driving. In addition, he had noted reduced libido for 10 years, intermittent headaches for 2 years and cold intolerance for 2 months. He shaved daily and had no other symptoms suggestive of endocrine dysfunction. Hypertension had been diagnosed 7 years previously and treated with oxprenolol. His previous health had otherwise been satisfactory. There was a family history of ischaemic heart disease but not of neurological or endocrinological problems.Examination revealed a corrected visual acuity of N/2 on the right and N/14 on the left, a bitemporal hemianopia, with a left lower quadrantic nasal field defect and bilateral pallor of the optic discs. He was moderately obese with nor- Initial investigations showed an increased cardiac diameter of 16cm without evidence of pulmonary oedema, a normal 12 lead ECG and normal plasma electrolytes, serum calcium, blood glucose and serum protein concentrations. Tests of endocrine function showed a serum prolactin concentration of 8180 mU/1 (normal range for males < 150) and a serum testosterone of 5-6 nmol/l (normal range for males 10-38). The results of other endocrine investigations were normal (table). A plain skull radiograph was normal without evidence of pituitary fossa enlargement or abnormal calcification and a CT brain scan revealed a non-enhancing, low density area in the left suprasellar region, with a normal sella. Bilateral carotid angiography showed an avascular space-occupying lesion in the suprasellar region with elevation and posterior displacement of the anterior cerebral arteries. As the radiological findings were consistent with a craniopharyngioma and the results of endocrine function tests were unavailable at that stage the lesion was explored, under hydrocortisone cover, using a subfrontal approach via a coronal flap. This revealed a cystic craniopharyngioma, confirmed histologically, which was subtotally resected leaving a fragment of the capsule which was adherent to the optic nerve. No tumour was seen arising from the sella.F...

The present study was initiated to examine the effect of pramiracetam sulfate [N-[B[bis(lrnethylethyl)amino]ethyl]-2 oxo-l-pyrrolidineacetamide sulfate (1 :1)] (PR), a new cognitionactivator agent, on various neurochemical parameters in order to gain some insight into the mechanism of action of this agent. PR (100 mg/kg i.p.) did not alter the concentration of norepinephrine, dopamine (DA), serotonin (5-HT), 5-hydroxyindoleacetic, and homovanillic acid in various brain areas. The agent also did not alter d-methamphetamine-induced changes in monoarnine metabolism nor prolactin concentration in rat serum. PR did not exhibit any affinity in vitro for doparninergic, adrenergic, serotoninergic, GABAergic, muscarinic, adenosine (ICs0 > 10 pM), and benzodiazepine receptors (ICs0 > 1 pM) binding sites. It may be concluded that the mechanism of action of pramiracetam does not appear to be due to a direct action upon DA and 5-HT neurotransmitter systems or various brain receptors. PR (44 and 88 mglkg i.p.) caused a significant increase in the rate of sodiumdependent high-affinity choline uptake (HACU) into rat hippocampal synptosomes in vitro. This was specific as no effect was observed in cerebral cortex and corpus striaturn. These results would seem to indicate that PR is accelerating hippocampal acetylcholine turnover and thus septal-hippocampal cholinergic neuronal impulse flow. This effect could be at least partially responsible for the enhancement of cognition processes observed for this agent.

Hemicastration in the rat is followed by hypertrophy of the remaining gonad (Heller, Heller & Sevringhaus, 1942), presumably as a result of increased pituitary secretion of gonadotrophins (Benson, Sorrentino & Evens, 1969). Howland (1972) food restriction of 50% was imposed and continued for 14 days; the animals were housed individually, the food intake of the intact and hemicastrated controls was measured daily and the experimental animals were fed 50% of these amounts. On the 15th day after the operation, the animals were killed and the left gonads from both the intact and hemicastrate rats were removed and weighed. Although different methods of observation from those of Howland (1972) were used, a 50% caloric restriction in the adult female prevented the ovarian compensatory hypertrophy; in the immature female, the hypertrophy was curtailed considerably. In the immature male rat, however, the gonadal hypertrophy was not affected (Table 1).Since the hemicastrated male showed gonadal hypertrophy when fed a restricted diet for 2 weeks, a preoperative period of dieting was also studied.Immature male rats were allocated to two groups. Those in one group were restricted in caloric intake 10 days before hemicastration and, in the other group, at the time of operation. In both groups, the restriction was continued for another 14 days. The experimental animals were compared to intact rats having similar dietary regimens (Table 2).At the time of the operation, the rats were 10 days older than those in the first experiment, which would account for the fact that the fully fed rats showed little or no gonadal hypertrophy. In those on a restricted intake for 14 and 24 159

The administration of the stable adenosine analogs N6-[(R)-methyl-2-phenylethyl]adenosine (R-PIA; 0.01-1.0 mg/kg i.p.) and 1-(6-amino-9H-purin-9-yl)-1-deoxy-N-ethyl-beta-D-ribofuronamide (NECA; 0.01-1.0 mg/kg i.p.) caused a dose-related (NECA) or biphasic (R-PIA) increases in rat serum prolactin. The S-isomer of PIA was inactive up to 4 mg/kg i.p. The methylxanthine aminophylline (10 and 30 mg/kg i.p.) antagonized the R-PIA- and NECA-induced elevation of prolactin suggesting an adenosine receptor-mediated effect. The dopaminergic agents L-dopa and bromocriptine antagonized the R-PIA and NECA-induced increase in serum prolactin. Haloperidol (a dopamine antagonist) and alpha-methyl-p-tyrosine (a catecholamine synthesis inhibitor) potentiated the R-PIA-induced effects. R-PIA and NECA did not displace 3H-haloperidol from rat striatal membranes nor effect in vitro prolactin release from rat anterior pituitary cells grown in culture. Based upon these findings it is postulated that R-PIA and NECA may be increasing prolactin secretion in part by inhibiting central dopamine release, although other mechanisms may also be operating.

The cell activation inhibitor CI-959 [5-methoxy-3-(1-methylethoxy)-N-1H-tetrazol-5-ylbenzo[ b]thiophene-2- carboxamide, monosodium salt] was evaluated for its effects on human neutrophil functions. CI-959 inhibited spontaneous migration and chemotaxis toward N-formyl-methionyl-L-leucyl-L-phenylalanine (fMLP) with 50% inhibition (IC50) values of 3.6 and 3.1 microM, respectively. CI-959 also inhibited superoxide anion generation in response to C5a, fMLP, serum-opsonized zymosan (SOZ), concanavalin A (Con A), and calcium ionophore A23187 with IC50 values of 2.5, 4.7, 14.5, 5.4, and 14.8 microM, respectively. In comparison, CI-959 inhibited myeloperoxidase microM, respectively. In comparison, CI-959 inhibited myeloperoxidase release in response to C5a, fMLP, SOZ, and Con A with IC50 values of 11.6, 16.1, 7.5, and < 1.0 microM, respectively, while inhibiting the response to A23187 by only 5.5% at 100 microM. At concentrations up to 100 microM, CI-959 had no effect on the respiratory burst or degranulation in response to L-alpha-1,2-dioctanoylglycerol (DiC8) or phorbol 12-myristate 13-acetate (PMA). In addition, the compound inhibited leukotriene B4 release stimulated by fMLP and SOZ (IC50 values 4.0 and 2.5 microM, respectively), while having less activity against the A23187-stimulated response (IC50 > 100 microM). These results demonstrate that CI-959 inhibits cellular responses to stimuli that mobilize intracellular calcium. For cellular responses to inophore-mediated calcium influx, only oxygen radical production was inhibited by CI-959. CI-959 was further evaluated for its effects on neutrophil stimulus-response coupling. At 100 microM, CI-959 had no effect on human neutrophil phospholipase C or protein kinase C. CI-959 inhibited fMLP-stimulated intracellular calcium mobilization and calcium influx with IC50 values of 16.7 and 3.1 microM, respectively, and exhibited less potent calmodulin antagonist activity (IC50 = 90.5 microM). These results indicate that CI-959 may exert its stimulus- and response-specific inhibitory effects on neutrophil functions, in part, through inhibition of calcium-regulated signalling mechanisms.