Novel Compounds Identified by Structure-Based Prion Disease Drug Discovery Using In Silico Screening Delay the Progression of an Illness in Prion-Infected Mice

The accumulation of abnormal prion protein (PrP^Sc) produced by the structure conversion of PrP (PrP^C) in the brain induces prion disease. Although the conversion process of the protein is still not fully elucidated, it has been known that the intramolecular chemical bridging in the most fragile pocket of PrP, known as the “hot spot,” stabilizes the structure of PrP^C and inhibits the conversion process. Using our original structure-based drug discovery algorithm, we identified the low molecular weight compounds that predicted binding to the hot spot. NPR-130 and NPR-162 strongly bound to recombinant PrP in vitro, and fragment molecular orbital (FMO) analysis indicated that the high affinity of those candidates to the PrP is largely dependent on nonpolar interactions, such as van der Waals interactions. Those NPRs showed not only significant reduction of the PrP^Sc levels but also remarkable decrease of the number of aggresomes in persistently prion-infected cells. Intriguingly, treatment with those candidate compounds significantly prolonged the survival period of prion-infected mice and suppressed prion disease-specific pathological damage, such as vacuole degeneration, PrP^Sc accumulation, microgliosis, and astrogliosis in the brain, suggesting their possible clinical use. Our results indicate that in silico drug discovery using NUDE/DEGIMA may be widely useful to identify candidate compounds that effectively stabilize the protein.Electronic supplementary materialThe online version of this article (10.1007/s13311-020-00903-9) contains supplementary material, which is available to authorized users.     

Low Phase Angle Is Correlated With Worse General Condition in Patients with Advanced Cancer

Objectives: Phase angle (PA) is a poor prognostic factor in patients with advanced cancer. This study aimed to identify possible correlations between PA and symptoms, quality of life, fluid retention, and laboratory data in cancer patients in palliative care settings.

Methods: Individuals who visited the outpatient clinic or were admitted to the palliative care unit were eligible. Patients with a performance status of 4 and/or those unable to complete questionnaires were excluded. PA was evaluated using a bioanalyzer device. The correlation coefficient between PA and the variables of interest was analyzed.

Results: A total of 102 patients were analyzed. PA was weakly correlated with age (ρ = ?0.22), performance status (ρ = ?0.30), functional well-being (ρ?=?0.20), anorexia/cachexia subscale (ρ?=?0.22), and Functional Assessment of Anorexia/Cachexia Therapy trial outcome index (ρ?=?0.26). PA was also correlated with fluid retention (ρ = ?0.34) and albumin (ρ?=?0.32), C-reactive protein (ρ = ?0.31), and hemoglobin (ρ?=?0.41) levels. Sub-analysis stratified according to sex revealed that males demonstrated the same results; however, female sex demonstrated a correlation between PA and social well-being (ρ = ?0.43).

Conclusions: PA was correlated with physical condition, but not with psychological well-being.     

Skeletal myoclonus in olivopontocerebellar atrophy: treatment with trihexyphenidyl

We studied two patients with nonfamilial olivopontocerebellar atrophy with skeletal myoclonus. Palatal or skeletal myoclonus is probably not a coincidental finding but another manifestation of the underlying disease. In both cases, the myoclonus was suppressed by administration of trihexyphenidyl, indicating a cholinergic disorder.     

Use of small-bore silastic drains in general thoracic surgery.

STUDY OBJECTIVE: To evaluate the safety and efficacy of small-bore, silastic drains for patients undergoing general thoracic surgery. PATIENTS AND METHODS: Twenty-five patients who received soft, small-bore, silastic drains were compared with 17 patients who received semi-rigid double lumen (DL) tubes retrospectively. RESULTS: The pain score was significantly lower in patients who received the silastic tubes in video-assisted thoracoscopic surgery (VATS) cases on postoperative days 5 and 6 , after continuous epidural analgesia had finished (P=0.018). No specific morbidity was seen in the patients who received silastic tubes. CONCLUSION: We considered that soft, small-bore silastic drains were just as effective as traditional DL tubes, but caused less pain especially in VATS cases.     

Pituitary stalk meningioma: case report

We report a 45-year-old woman with a meningioma which was in contact with only the pituitary stalk on MRI. As the pituitary stalk has no dura mater, we suggest this tumour may have originated from the arachnoid membrane of the pituitary stalk. Though some reports have shown that meningiomas can arise from sites lacking a dural component, this is the first report of a meningioma originating from the pituitary stalk. Received: 21 December 1995 Accepted: 26 February 1996     

Plasma atrial natriuretic peptide during hemodialysis with or without fluid removal

Plasma immunoreactive human atrial natriuretic peptide (hANP) levels were measured in 9 patients with chronic renal failure treated with maintenance hemodialysis in order to evaluate the effects of fluid removal and osmotic pressure. Under hemodialysis without fluid removal plasma hANP levels remained unchanged, but the levels were significantly decreased during extra-corporeal ultrafiltration (p less than 0.01). The present study provided strong evidence that the fall in plasma hANP levels in hemodialysis patients is mainly due to the reduction in circulating plasma volume.