Alpha7 nicotinic acetylcholine receptor-specific agonist DMXBA (GTS-21) attenuates Aß accumulation through suppression of neuronal γ-secretase activity and promotion of microglial amyloid-ß phagocytosis and ameliorates cognitive impairment in a mouse model of Alzheimer's disease.

We previously demonstrated that stimulation of nicotinic acetylcholine receptors (nAChRs) increases amyloid-ß (Aß) phagocytosis in rat microglia and is closely associated with the decrease of brain Aß and amelioration of memory dysfunction in a transgenic mouse model of Alzheimer's disease (AD). Here, we examined the subtypes of nAChRs involved in these beneficial effects. In primary cultures of rat microglia, the α7 nAChR selective agonist 3-[(2,4-dimethoxy)benzylidene]-anabaseine dihydrochloride (DMXBA) promoted Aß and fluorescent latex bead phagocytosis, whereas selective α7 nAChR antagonists suppressed the enhanced Aß phagocytosis. In a transgenic mouse model of AD, administration of DMXBA attenuated brain Aß burden and memory dysfunction. Moreover, DMXBA suppressed γ-secretase activity in solubilized fractions of human neuroblastoma cells and transgenic mouse brain. These results suggested that selective activation of α7 nAChRs promoted microglial Aß phagocytosis and suppressed neuronal γ-secretase activity to contribute to the attenuation of the brain Aß burden and cognitive impairment. Thus, we propose neuronal and microglial α7 nAChRs as new therapeutic targets in the treatment of AD.

Reliability of laparoscopic skills assessment on video: 8-year results of the endoscopic surgical skill qualification system in Japan.

BACKGROUND AND PURPOSE: The Japanese Urological Association and Japanese Society of Endourology established a urologic laparoscopic skills qualification system called the Endoscopic Surgical Skill Qualification (ESSQ) System in Urological Laparoscopy in 2004. The reliability of video assessments by referees was evaluated. MATERIALS AND METHODS: Videos of nephrectomies or adrenalectomies performed by the applicants were assessed by two referees selected among a pool of 42 referees. From 2004 to 2011, 1308 urologists applied and 60.2% were qualified after video assessments. The results of skills assessments on 1220 videos that had fixed points by two referees were analyzed statistically. RESULTS: The average number of videos that each referee assessed was 58.1, with a range of 16 to 87. The accordance rate of the results of the video assessment, pass or fail, by the two referees was 68.9%. The scores of the video assessment by each referee averaged 62.7±2.4 (standard deviation) (full score was set at 75 points and ≥60 points was needed to pass). There was a statistically significant difference in the average video assessment score among the referees (P<0.001), and five referees showed significantly higher or lower average scores than the other referees. The percentage qualification of the final decision made by the Referee Committee on the videos originally assessed by each referee showed no significant differences among the 42 referees. The accordance rate of the results from the video assessment by each referee with the final decision by the committee showed a statistically significant positive correlation with the number of videos assessed by each referee (r=0.404, P=0.0080). CONCLUSIONS: The ESSQ system showed moderate reliability for the video assessments by the referees. It was concluded that the video assessments by the referees were fair for all applicants, because the final qualification rates showed no significant differences among the referees.

Transurethral ethanol injection for prostatic obstruction: an excellent treatment strategy for persistent urinary retention.

OBJECTIVES: To evaluate the efficacy of transurethral ethanol injection into the prostate (TUEIP) for patients with persistent urinary retention resulting from benign prostatic hyperplasia or advanced prostate cancer. METHODS: Twenty-one Japanese men (elderly or at high risk anesthesiologically) who had developed persistent urinary retention because of benign prostatic hyperplasia or advanced prostate cancer were treated with TUEIP from January 2001 to January 2005. Patient age and preoperative prostate volume was 64 to 92 years (median 84) and 24.1 to 125 cm3 (mean 57.6), respectively. Under sacral or lumbar anesthesia, 6 to 14 mL (mean 10.6) of dehydrated ethanol (mean ratio for prostate volume 22.7%) was injected into the prostate under endoscopic guidance, followed by placement of an indwelling catheter. RESULTS: Of the 16 patients with benign prostatic hyperplasia and 5 with advanced prostate cancer, 14 (87.5%) and 3 (60%), respectively, were able to void spontaneously after catheter removal. The catheter had been left in place for 7 to 37 days (mean 12.4) after surgery. No additional treatment was required during the 2 to 24 months (mean 16) of follow-up. The postoperative residual urine volume of these 17 patients was 20 to 150 mL (mean 60) and their mean prostate volume had decreased from 52.7 to 37.9 cm3 (28.1% reduction) at 6 months postoperatively (P <0.001). No major complication was experienced. CONCLUSIONS: In patients with persistent urinary retention due to prostatic obstruction without severe complications, TUEIP removes the need for catheterization and allows spontaneous voiding. TUEIP may be an alternative to transurethral resection of the prostate for high-risk or elderly patients who cannot tolerate surgery.

[Ureteral cancer producing granulocyte colony-stimulating factor: a case report].

A 60-year-old man who underwent radical nephroureterectomy due to left ureteral cancer 22 months before (transitional cell carcinoma, pT4pN0Mx, grade 2, INF beta), was admitted to the hospital with the chief compliant of anorexia and body weight loss. The patient had severe leukocytosis and elevation of C-reactive protein, with no obvious focus of infection. Abdominal plain computed tomographic scan revealed left external ileac lymph node swelling. Positron emission tomography demonstrated left external ileac lymph node recurrence. Enzyme immunoassay of the serum demonstrated a markedly high concentration of granulocyte colony-stimulating factor (G-CSF; 790 pg/ml). Immunohistochemical examination of ureteral cancer cells with anti-G-CSF monoclonal antibody demonstrated G-CSF production in cancer cells. After diagnosed as lymph node recurrence of ureteral cancer producing G-CSF, the patient underwent radiotherapy (total 4000 Gy). CT after radiotherapy showed the complete disappearance of the lymph node swelling. To our knowledge, this is the second report of ureteral cancer proven to produce G-CSF in Japan.