Expression of neprilysin,somatostatin and the somatostatin sst5 receptor in the hippocampal formation of brains from Alzheimer's disease patients

Background: In Alzheimer's disease (AD), the accumulation of amyloid β (Aβ) in the brain is thought to be the primary pathogenic agent in the AD cascade. The following have been proposed as potential therapeutic strategies in AD: (i) protease inhibitors, including β secretase and γ secretase; (ii) Aβ vaccination; and (iii) inhibitors of Aβ agglutination. However, as yet there are no studies demonstrating successful suppression of Aβ accumulation in AD brains. Neprilysin (NEP), a neutral endopeptidase, is a major Aβ‐degrading enzyme that is activated by somatostatin (SST). It is thought that NEP may be a therapeutic agent against AD, but the role of SST in AD brains has not been sufficiently elucidated to date. Thus, in the present study, we compared the expression of SST, the sst₅ receptor, and NEP in the hippocampal formation in brains from both AD patients and normal controls using immunohistochemical techniques. Methods: Twelve human brains (six control brains and six AD brains) were used in the present study. The diagnosis of AD was made according to the Braak stage. Control brains were selected from cases with no cognitive impairment clinically that were classified as being at Braak neurofibrillary tangle (NFT) Stage II. The AD brains were selected from cases classified as greater than Braak NFT Stage IV. Results: In the present study, SST and sst₅ receptor‐like immunoreactivity was significantly reduced in AD brains compared with normal brains. Although NEP‐like immunoreactivity was also significantly reduced in AD brains compared with normal brains, in the CA4 region NEP was preserved in the hippocampal formation of AD brains. Conclusion: These results suggest that the origin of the Aβ accumulated may be correlated with the reduction of the SST neuronal network in AD brains. Activating intrinsic NEP through the SST neuronal system may contribute to a reduction in the risk of AD. Further investigations into the role SST receptors may provide new pharmacotherapeutic strategies for the treatment of AD.     

Presenile dementia mimicking Pick's disease: An autopsy case of localized amygdala degeneration with character change and emotional disorder

This report concerns an autopsy case showing localized amygdala degeneration. The patient was a Japanese single woman without hereditary burden who was 58 years old at the time of death. At the age of 55 years, the patient began to feel anxiety, agitation and depressive in mood. At age 58 years, she developed marked character changes and emotional disorders, although disorientation and memory disturbance were slight. We suspected her disease was a variant of presenile dementia, especially Pick's disease, and some neuroradiological examinations disclosed bilateral temporal involvements. We could not make a definitive diagnosis from the clinical findings. She choked to death 3 years after the disease onset. From the neuropathological examinations, the known neurodegenerative diseases causing dementia, including Pick's disease, were excluded and we diagnosed our case as having localized amygdala degeneration. Localized amygdala degeneration itself is very rare. Moreover, in this case, the amygdala degeneration was presumed to be idiopathic, without any apparent cause. To our knowledge, this is the first case of idiopathic localized amygdala degeneration. This case indicates that localized amygdala degeneration can cause presenile dementia, and that character changes and emotional disorders are predominant over memory disturbance and/or disorientation.     

Risk factors influencing the short-term results of gastroduodenal perforation

The purpose of this study was to evaluate the risk factors influencing the short-term results of gastroduodenal perforation to determine the optimal treatment for reducing mortality. A total of 136 patients were retrospectively reviewed and the prognostic factors were examined. Seven patients died within 30 days, with an overall mortality rate of 5.1%. Mortality was significantly worse in those aged 50 years or more, when the leukocyte count was less than 9,500/mm³, when treatment was delayed more than 12 h after perforation, in cases of preoperative shock and renal failure, and when associated with liver cirrhosis or an immunocompromised state. Tolerance to the time delay was inversely proportional to age, while the deaths in patients aged 65 years or younger were related to serious concurrent diseases. Shock and renal failure occurred most often in elderly patients as a result of delayed surgery, and the leukocyte count was an age-dependent prognostic indicator. Thus, age, the time interval between perforation and treatment, serious concurrent disease, shock, and renal failure were presumed to be the most important prognostic factors. Although definitive operations were performed on low-risk patients with an acceptably low mortality, it remains to be determined whether simpler procedures should be adopted for high-risk patients.     

CNS Changes in DRPLA with Dementia and Personality Changes: CT, MR and SPECT Findings

Abstract: CNS changes in a case of DRPLA associated with dementia and personality changes were observed by CT, MR and SPECT. Brain CT and MR of the patient revealed progressive cortical atrophy which was recognized in parallel with the clinical course of the progression of dementia and personality changes. SPECT using ¹²³I-iodoamphetamine (IMP) disclosed a diffuse low perfusion of the cerebral cortex, especially in the frontal and temporal lobes. These findings suggest that the dementia and personality changes in this case might be concerned with a dysfunction of the cerebral cortex.     

Primary volvulus of the small intestine in infants

Primary small bowel volvulus which no definite cause can be detected surgically is rare. In this paper, we present five cases of primary small bowel volvulus and discuss the clinical features including etiology.     

Efficacy and safety of aprepitant in patients with breast cancer

We retrospectively analyzed the efficacy and safety of aprepitant in breast cancer patients who were treated with FEC(5- fluorouracil, epirubicin, cyclophosphamide)or EC(epirubicin, cyclophosphamide). We divided patients into two groups according to the aprepitant approval period. The rate of severe nausea(@Grade 2)was significantly less in patients with aprepitant(acute 10. 0%, delayed 15. 0%)than those without aprepitant(acute 29. 1%, delayed 30. 9%). Complete response( no vomiting and no use of rescue therapy)in the acute phase was significantly higher in the aprepitant pretreated group than in the no aprepitant group(82. 5% vs 61. 8%, respectively). Moreover, complete response in the delayed phase was also higher in the aprepitant group than in the no aprepitant group(82. 5%vs 58. 2%, respectively). Pre-treatment with aprepitant did not increase adverse events including constipation and elevation of alanine transaminase. The aprepitant was effective in terms of prevention of chemotherapy-induced nausea and vomiting in patients treated with an anthracycline- based regimen.     

DLL3 regulates the migration and invasion of small cell lung cancer by modulating Snail

Delta‐like protein 3 (DLL3) is a ligand of Notch signaling, which mediates cell‐fate decisions and is tumor‐suppressive or oncogenic depending on the cellular context. Previous studies show that DLL3 is highly expressed in small cell lung cancer (SCLC) but not in normal lung tissue, suggesting that DLL3 might be associated with neuroendocrine tumorigenesis. However, its role in SCLC remains unclear. To investigate the role of DLL3 in tumorigenesis in SCLC, we performed loss‐of‐function and gain‐of‐function assays using SCLC cell lines. In vitro analysis of cell migration and invasion by transwell assay showed that DLL3 knockdown reduced migration and invasion of SCLC cells, whereas DLL3 overexpression increased these activities. In addition, DLL3 positively regulated SNAI1 expression and knockdown of SNAI1 attenuated the migration and invasion ability of SCLC cells. Moreover, upregulated DLL3 expression induced subcutaneous tumor growth in mouse models. These results indicate that DLL3 promoted tumor growth, migration and invasion in an SCLC model by modulating SNAI1/Snail.     

Petrous bone cholesteatoma removed by trans-superior semicircular canal approach: long-term hearing results in three cases

The aim of this report is to describe the long-term hearing prognosis of the transmastoid trans-superior semicircular canal approach. Three patients with small petrous bone cholesteatoma of the supralabyrinthine type removed by partial removal of the superior semicircular canal (SSCC) were followed up for 13, 9, and 10 years, respectively. All patients showed good bone conduction hearing during the follow-up period without postoperative complications, including longstanding disequilibrium causing a reduction in the quality of life. As an approach to petrous bone cholesteatoma of supralabyrinthine type that occupies a small area medial to the SSCC, the transmastoid trans-superior semicircular canal approach is less invasive and is considered to be a recommended approach.