Glavonoid, a possible supplement for prevention of ATTR amyloidosis.

Transthyretin (TTR) is an amyloidogenic protein associated with hereditary and nonhereditary transthyretin amyloidoses (ATTR). Dissociation of the tetramer of TTR to the monomer induces TTR misfolding, which leads to amyloid fibril formation and triggers the onset of ATTR amyloidosis. Stabilizers of tetrameric TTR have been accepted as an effective ATTR amyloidosis treatment while effect is limited and they are too expensive. The aim of our study was to find more effective and cheep natural compound to suppress TTR amyloid formation. Glabridin, a prenylated isoflavan isolated from Glycyrrhiza glabra L., stabilized the TTR tetramer in vitro. The effects of licorice-derived flavonoid oil-Glavonoid, a natural substance that includes glabridin and several polyphenols-on stabilizing the TTR tetramer must still be elucidated. To examine plasma TTR stabilization by Glavonoid in vitro, we investigated the feasibility of utilizing glabridin plus Glavonoid to prevent TTR amyloid fibril formation. Glavonoid mixed with human plasma samples at 24 h incubation in vitro increased the tetramer level (P < 0.05) and reduced the monomer level (P < 0.01) and the monomer/tetramer ratio (P < 0.05) of TTR compared to those without Glavonoid by immunoblot analysis, such effect could not observe in the presence of glabridin. Oral Glavonoid (300 mg for 12 weeks) in 7 healthy volunteers effectively increased the plasma glabridin concentration. Glavonoid increased the TTR tetramer level and reduced the monomer/tetramer ratio of TTR (P < 0.05) in plasma at 12 weeks in healthy volunteers compared to those of age matched control subjects without the supplement. Thus, oral Glavonoid may effectively prevent TTR amyloid fibril formation via TTR tetramer stabilization. Glavonoid may become a promising supplement before onset of ATTR amyloidosis.

Amyloid fibril formation is suppressed in microgravity.

In the future, humans may live in space because of global pollution and weather fluctuations. In microgravity, convection does not occur, which may change the amyloidogenicity of proteins. However, the effect of gravity on amyloid fibril formation is unclear and remains to be elucidated. Here, we analyzed the effect of microgravity on amyloid fibril formation of amyloidogenic proteins including insulin, amyloid ß42 (Aß42), and transthyretin (TTR). We produced microgravity (10-3 g) by using the gravity controller Gravite. Human insulin, Aß42, and human wild-type TTR (TTRwt) were incubated at pH 3.0, 7.0, and 3.5 at 37 °C, respectively, in 1 g on the ground or in microgravity. We measured amyloidogenicity via the thioflavin T (ThT) method and cell-based 1-fluoro-2,5-bis[(E)-3-carboxy-4-hydroxystyryl]benzene (FSB) assay. ThT fluorescence intensity and cell-based FSB assay results for human insulin samples were decreased in microgravity compared with results in 1 g. Aß42 samples did not differ in ThT fluorescence intensity in microgravity and in 1 g on the ground. However, in the cell-based FSB assay, the staining intensity was reduced in microgravity compared with that on 1 g. Human TTRwt tended to form fewer amyloid fibrils in ThT fluorescence intensity and cell-based FSB assays in microgravity than in 1 g. Human insulin and Aß42 showed decreased amyloid fibril formation in microgravity compared with that in 1 g. Human TTRwt tended to form fewer amyloid fibrils in microgravity. Our experiments suggest that the earth's gravity may be an accelerating factor for amyloid fibril formation.

[Need for Prescription Suggestions for Long-term Inpatients in the Psychiatric Ward].

Additional fees for ward pharmacists' services have been valued for hospitals in Japan. However, the calculation period for services provided to inpatients in the psychiatric ward is limited to 8 weeks. This study aimed to reveal the need for the services of pharmacists in the hospital ward for inpatients hospitalized for >8 weeks in the psychiatric ward. Patients who were hospitalized in the psychiatric ward from September 2016 to February 2017 were analyzed retrospectively. The pharmacists suggested prescriptions for inpatients admitted for >8 weeks, similar to those admitted for <9 weeks, and this supported pharmacotherapy without exacerbating patient outcomes. Moreover, significant decreases in benzodiazepine doses were found between the prior and post prescription suggestions of the pharmacist for inpatients >8 weeks of admission. Healthcare expenditures were also reduced. These results suggest that the prescriptions suggested by pharmacists for inpatients admitted for >8 weeks in the psychiatric ward were useful. In conclusion, our findings show that ward pharmacists' services were necessary not only for the inpatients hospitalized for <9 weeks, but also for those hospitalized for >8 weeks.

Effect of Patient Education for Diabetic Outpatients by a Hospital Pharmacist: A Retrospective Study.

The number of patients with diabetes continues to increase in Japan, which means that education in disease management is important. However, there have been few investigations into the importance of hospital pharmacists performing outpatient education for diabetes mellitus in Japan. In the diabetes outpatient department of Kitakyushu City Moji Hospital, a pharmacist commenced patient education using check sheets before patients saw the physicians from 2012. We divided the patients into groups with an increase or decrease of hemoglobin A1c (HbA1c) level after 6 months from the start of patient education. To assess the factors related to a decrease of HbA1c level, we compared background factors, and laboratory values between these two groups. In the patients whose HbA1c level decreased, the level was high at the start of patient education and they had less knowledge about their medications. To evaluate the impact of this patient education, we compared HbA1c values before patient education and after 6 months to determine the effect of providing education in the diabetes outpatient department. In the HbA1c≥8% group, the HbA1c level decreased significantly during 6 months of patient education. These results suggest that patient education by hospital pharmacists can be effective if HbA1c level is high at the start of education. This is the first report about the usefulness of patient education by a hospital pharmacist for improvement of HbA1c level in diabetic outpatients in Japan.