Object: The increase in the incidental detection of asymptomatic pituitary adenomas, known as “pituitary inciden-talomas,” led the authors to conduct a survey of the natural course of these lesions. Methods: Forty-two patients with clinically nonfunctioning pituitary adenomas who had manifested no neurological or endocrinological disorders were monitored with magnetic resonance imaging studies. The follow-up period ranged from 10.8 to 168.2 months (mean ± standard deviation, 61.9 ± 38.2 months). The mean initial tumor size was 18.3 ± 7 mm. In 21 patients, the tumor increased by at least 10% of its measured size on detection. This increase was first detected between 8.4 and 58.8 months (mean 31.8 ± 17.6 months) after diagnosis. There was no correlation between the original tumor size, patient age, or the presence of intratumoral cysts and tumor growth. Symptoms were noted in 10 patients during follow up; in four, extensive tumor necrosis accompanied hemorrhage, leading to severe headache, acute ophthalmological symptoms, and panhypopituitarism, which was indicative of pituitary apoplexy. Transsphenoidal surgery was performed in 12 patients with enlarged tumors, including three with apoplexy. With the exception of one apoplectic patient, visual function was recovered in all who underwent surgery. All apoplectic patients continue to manifest hypopituitarism. Conclusions: In the course of 4 years, the size of the incidentalomas increased in 40% of 42 patients and became symptomatic in 20%. During the 5-year follow up, pituitary apoplexy developed in 9.5%. These findings may justify early intervention, especially in young individuals with incidentally found macroadenoma.

Levodopa‐induced dyskinesia has been suggested to result from maladaptive plasticity at corticostriatal synapses. Synaptic plasticity is based upon morphologic changes of dendritic spines. To elucidate whether the morphologic changes of spines occur in the striatum of rat models of levodopa‐induced dyskinesia, we examined immunoreactivity of drebrin, an actin‐binding protein localized in dendritic spines of excitatory synapses, using 6‐hydroxydopamine‐lesioned rats repeatedly treated with levodopa. The cross‐sectional area of drebrin‐immunoreactive organelles, putative spines, in the dopamine‐denervated striatum of the levodopa‐induced dyskinesia model was greater than that of the Parkinson's disease model. Immunoelectron microscopic examinations confirmed that drebrin‐immunoreactive spines became enlarged in the dopamine‐denervated striatum of the levodopa‐induced dyskinesia model, but not in the Parkinson's disease model. These results suggest that the development of levodopa‐induced dyskinesia is associated with enlargement of dendritic spines at corticostriatal excitatory synapses.

P2X7 receptors (P2X7Rs) are ATP-gated ion channels that display the unusual property of current facilitation during long applications of agonists. Here we show that facilitation disappears in chimeric P2X7Rs containing the C-terminus of the P2X2 receptor (P2X2R), and in a truncated P2X7R missing the cysteine-rich domain of the C-terminus. The chimeric and truncated receptors also show an apparent decreased permeability to N-methyl-d-glucamine⁺ (NMDG⁺). The effects of genetic modification of the C-terminus on NMDG⁺ permeability were mimicked by preapplication of the HSP90 antagonist geldanamycin to the wild-type receptor. Further, the geldanamycin decreased the shift in the reversal potential of the ATP-gated current measured under bi-ionic NMDG⁺/Na⁺ condition without affecting the ability of the long application of agonist to facilitate current amplitude. Taken together, the results suggest that HSP90 may be essential for stabilization and function of P2X7Rs through an action on the cysteine-rich domain of the cytoplasmic the C-terminus.

The role of the GABA(B) receptor in the anterior cingulate cortex (ACC) of neuropathic pain is unclear. Injection of a GABA(B) receptor antagonist CGP35348 into the ACC induced mechanical hypersensitivity in normal rats. Activation of the GABA(B) receptor injected by a GABA(B) receptor agonist baclofen into the ACC attenuated mechanical hypersensitivity in partial sciatic nerve ligation (PSNL) rats. Co-microinjection of CGP35348 with a muscarinic M1 receptor agonist McN-A-343 into the ACC significantly inhibited McN-A-343-induced antihypersensitivity in PSNL rats. These results suggest that the GABA(B) receptor in the ACC contributes to mechanical hypersensitivity and is involved in muscarinic M1 receptor-mediated antihypersensitivity. (c) 2018 The Authors. Production and hosting by Elsevier B.V. on behalf of Japanese Pharmacological Society.