BACKGROUND: With rising worldwide population aging, the number of homebound individuals with multimorbidity is increasing. Improvement in the quality of home medical care (HMC), including medications, contributes to meeting older adults' preference for "aging in place" and securing healthcare resources. OBJECTIVE: To evaluate the changes in drug prescriptions, particularly potentially inappropriate medications (PIMs), among older adults receiving HMC in recent years, during which measures addressing inappropriate polypharmacy were implemented, including the introduction of clinical practice guidelines and medical fees for deprescribing. DESIGN: A cross-sectional study. PARTICIPANTS: Using data from the national claims database in Japan, this study included older adults aged <= 75 years who received HMC in October 2015 (N = 499,850) and October 2019 (N = 657,051). MAIN MEASURES: Number of drugs, prevalence of polypharmacy (<= 5 regular drugs), major drug categories/classes, and PIMs according to Japanese guidelines were analyzed. Random effects logistic regression models were used to evaluate the differences in medications between 2015 and 2019, considering the correlation within individuals who contributed to the analysis in both years. KEY RESULTS: The number of drugs remained unchanged from 2015 to 2019 (median: 6; interquartile range: 4, 9). The prevalence of polypharmacy also remained unchanged at 70.0% in both years (P = 0.93). However, the prescription of some drugs (e.g., direct oral anticoagulants, new types of hypnotics, acetaminophen, proton pump inhibitors, and beta-blockers) increased, whereas others (e.g., warfarin, vasodilators, H2 blockers, acetylcholinesterase inhibitors, and benzodiazepines) decreased. Among the frequently prescribed PIMs, benzodiazepines/Z-drugs (25.6% in 2015 to 21.1% in 2019; adjusted odds ratio: 0.52) and H2 blockers (11.2 to 7.3%; 0.45) decreased, whereas diuretics (23.8 to 23.6%; 0.90) and antipsychotics (9.7 to 10.5%; 1.11) remained unchanged. CONCLUSIONS: We observed some favorable changes but identified some continuous and new challenges. This study suggests that continued attention to medication optimization is required to achieve safe and effective HMC.
Title: Non-coding RNA Neat1 and Abhd11os expressions are dysregulated in medium spiny neurons of Huntington disease model mice Park H, Miyazaki H, Yamanaka T, Nukina N Ref: Neurosci Res, 147:58, 2019 : PubMed
Huntington Disease (HD) is a neurodegenerative disorder caused by expanded CAG repeats in the exon1 of huntingtin gene (HTT). The mutant HTT affects the transcriptional profile of neurons by disrupting the activities of transcriptional machinery and alters expression of many genes. In this study, we identified dysregulated non-coding RNAs (ncRNAs) in medium spiny neurons of 4-week-old HD model mouse. Also, we observed the intracellular localizations of Abhd11os and Neat1 ncRNAs by ViewRNA in situ hybridization, which could provide more precise detection, suggesting that it is a useful method to investigate the expression changes of genes with low expression levels.
Title: Functional expression of choline transporter-like protein 1 (CTL1) in small cell lung carcinoma cells: A target molecule for lung cancer therapy Inazu M, Yamada T, Kubota N, Yamanaka T Ref: Pharmacol Res, 76C:119, 2013 : PubMed
Choline is essential for the synthesis of the major membrane phospholipid phosphatidylcholine and the neurotransmitter acetylcholine (ACh). Elevated levels of choline and up-regulated choline kinase activity have been detected in cancer cells. Thus, the intracellular accumulation of choline through choline transporters is the rate-limiting step in phospholipid metabolism and a prerequisite for cancer cell proliferation. However, the uptake system for choline and the functional expression of choline transporters in lung cancer cells are poorly understood. We examined the molecular and functional characterization of choline uptake in the small cell lung carcinoma cell line NCI-H69. Choline uptake was saturable and mediated by a single transport system. Interestingly, removal of Na+ from the uptake buffer strongly enhanced choline uptake. This increase in choline uptake under the Na+-free conditions was inhibited by dimethylamiloride (DMA), a Na+/H+ exchanger (NHE) inhibitor. Various organic cations and the choline analog hemicholinium-3 (HC-3) inhibited the choline uptake and cell viability. A correlation analysis of the potencies of organic cations for the inhibition of choline uptake and cell viability showed a strong correlation (R=0.8077). RT-PCR revealed that choline transporter-like protein 1 (CTL1) mRNA and NHE1 are mainly expressed. HC-3 and CTL1 siRNA inhibited choline uptake and cell viability, and increased caspase-3/7 activity. The conversion of choline to ACh was confirmed, and this conversion was enhanced under Na+-free conditions, which in turn was sensitive to HC-3. These results indicate that choline uptake through CTL1 is used for ACh synthesis. Both an acetylcholinesterase inhibitor (eserine) and a butyrylcholinesterase inhibitor (ethopropazine) increased cell proliferation, and these effects were inhibited by 4-DAMP, a mAChR3 antagonist. We conclude that NCI-H69 cells express the choline transporter CTL1 which uses a directed H+ gradient as a driving force, and its transport functions in co-operation with NHE1. This system primarily supplies choline for the synthesis of ACh and secretes ACh to act as an autocrine/paracrine growth factor, and the functional inhibition of CTL1 could promote apoptotic cell death. Identification of this new CTL1-mediated choline transport system provides a potential new target for therapeutic intervention.
OBJECTIVE: Several studies have shown glycated albumin (GA) to be a more accurate glycemic marker than HbA(1c) in diabetic patients with end-stage renal disease (ESRD). However GA values are influenced by several factors associated with albumin turnover independent of glycemia. We tried to clarify the factors other than glycemic control affecting GA values in ESRD patients. PATIENTS AND METHODS: We examined the associations between GA values and several clinical variables related to albumin metabolism in 41 non-diabetic patients on maintenance hemodialysis. RESULTS: Although there were no significant correlations between glucose, albumin, and GA values, there were significant correlations between age, cholinesterase (ChE) values, BMI, and GA values (r=0.515, p=0.0004, r=-0.394, p=0.010, r=-0.327, p=0.036). Stepwise multivariate regression analysis showed that age and ChE values were significant independent variables associated with GA values (beta=0.479, -0.343, R(2)=0.382). CONCLUSION: GA values are influenced by age and nutritional status independent of glycemia in non-diabetic ESRD patients. We should be aware of factors other than glycemic control affecting GA values.
Title: Characterization of serum platelet-activating factor (PAF) acetylhydrolase. Correlation between deficiency of serum PAF acetylhydrolase and respiratory symptoms in asthmatic children Miwa M, Miyake T, Yamanaka T, Sugatani J, Suzuki Y, Sakata S, Araki Y, Matsumoto M Ref: J Clinical Investigation, 82:1983, 1988 : PubMed
Platelet-activating factor (PAF) acetylhydrolase has been recognized as an enzyme that inactivates PAF. We developed a convenient and reproducible method for determining human serum PAF acetylhydrolase activity. The assay was based on measurement of [14C]acetate produced from 1-O-alkyl-2-[14C]-acetyl-sn-glycero-3-phosphocholine upon precipitation of the complex of radioactive substrate and albumin with TCA. The apparent Km value of PAF acetylhydrolase (near the physiological concentration of serum protein) was 1.5 X 10(-4) M PAF. 32 subjects with serum PAF acetylhydrolase deficiency were found among 816 healthy Japanese adults. The low PAF acetylhydrolase activity in the deficient serum might not be due to the presence of enzyme inhibitor. Both the sensitivity to PAF and the metabolism of PAF in platelets from PAF acetylhydrolase-deficient subjects were almost the same as those of normal subjects. Deficiency in serum PAF acetylhydrolase appeared to be transmitted by autosomal recessive heredity among five Japanese families. Among healthy adults, healthy children, and asthmatic children, who were grouped into five classes on the basis of respiratory symptoms (remission, wheezy, mild, moderate, and severe groups), the probability of PAF acetylhydrolase deficiency was significantly higher in groups with severe symptoms (moderate and severe) (P less than 0.01). These results suggest that deficiency of serum PAF acetylhydrolase might be one of the factors leading to severe respiratory symptoms in asthmatic children.
