[Life, mental, and social functional factors associated with a decreased activity in elderly requiring support/care].

AIM: To clarify the factors associated with a decreased activity in elderly requiring support/care. METHODS: We included 340 of the 671 people receiving outpatient rehabilitation services under the long-term care insurance system in the present study. These subjects were classified as the favorable motor function group, based on the findings from previous studies, as they required ≤12 seconds to complete the Timed Up & Go test (TUG) task. All of the subjects agreed to participate in the study. The study items were as follows: the LSA score; age; sex; diagnosis name; care grade; number of family members living together; number of times the service was used; TUG score; hand grip strength; scores from the Tokyo Metropolitan Institute of Gerontology Index of Competence, Fall Efficacy Scale (FES), Geriatric Depression Scale Short-Version (Japanese), subjective health, and Japanese version of the Six-item Lubben Social Network Scale score; hobbies; role in the household; availability of nearby public transportation services; presence of accessible supermarkets; and presence of pain. On a statistical analysis, we divided the subjects into 2 groups based on their LSA scores: those with a decreased activity (<56) and those with a favorable function/activity (≥56). We then conducted the unpaired t-test and chi-square test to examine these binary variables. Subsequently, we performed a multiple logistic regression analysis with the binary variables as dependent variables. For statistical processing, we used the SPSS Statistics software program, ver. 25, and set the significance level at <5%. RESULTS: Among the 340 subjects, 139 and 201 were categorized as the decreased activity and favorable function/activity groups, respectively. Through a multiple logistic regression analysis, we obtained the following odds ratios: Instrumental Activities of Daily Living (IADL), 0.608 (95% confidence interval: 0.453-0.816); FES, 0.908 (0.855-0.963); and availability of nearby public transportation services, 0.619 (0.390-0.982). CONCLUSIONS: These results suggested the feasibility of identifying factors associated with decreased activity by appropriately conducting assessments using the IADL and FES and availability of nearby public transportation services.

Enhanced susceptibility of LDL to oxidative modification in a CTX patient:- role of chenodeoxycholic acid in xanthoma formation.

Cerebrotendinous xanthomatosis (CTX) is a rare familial sterol storage disease, causing multiple xanthomas in tendons and the brain. The underlying biochemical defect is a lack of the hepatic mitochondrial cholesterol 27-hydroxylase involved in the normal biosynthesis of bile acid, resulting in reduced biosynthesis of chenodeoxycholic acid (CDCA). It has been reported that administration of CDCA to CTX patients improves neurological disorders and xanthomas of the Achilles tendon. The present study investigated the effect of CDCA on the mechanism of cholesterol accumulation in macrophages, the major cells in xanthoma. The LDL from the patients in this study was significantly more susceptible to oxidative modification than normal LDL, and supplement therapy with CDCA resulted in an improvement in the susceptibility to oxidative modification. In the incubation of CDCA with plasma, 13% of the CDCA added to serum was recovered in the LDL fraction. In addition, supplementation with CDCA enhanced cholesteryl ester transfer protein (CETP) activity and reduced high-density-lipoprotein cholesterol levels in the plasma. This evidence suggests that the multiple xanthomas observed in CTX may be induced by increased oxidized LDL and the low activity of CETP, both of which are caused by a lack of CDCA.

Scavenger receptor type BI potentiates reverse cholesterol transport system by removing cholesterol ester from HDL.

High-density lipoprotein (HDL) plays an important role in reverse cholesterol transport by removing accumulated cholesterol from extrahepatic tissues. Subsequently, cholesterol ester (CE) on HDL in humans is transported to apolipoprotein B-containing lipoproteins by cholesteryl ester transfer protein (CETP). CETP deficiency, which is common in the Japanese population, leads to a marked increase in HDL-cholesterol levels due to impaired CE transport from HDL to LDL. It has been reported that the HDL observed in CETP deficiency is an atherogenic lipoprotein, as it contains a large amount of CE. Scavenger receptor class B type I (SR-BI) has been found to be an authentic HDL receptor that mediates the selective uptake of HDL CE and the bi-directional transfer of free cholesterol between HDL and cells. In the present study, the interaction between SR-BI and CE-rich HDL from CETP-deficient patient was studied in order to evaluate the anti-atherosclerotic role of SR-BI in relation to CE uptake and reverse cholesterol transport. When CE-rich HDL was added to the medium of SR-BI-transfected CHO (SR-BI CHO) cells, more CE accumulated in SR-BI CHO cells compared to control HDL. In contrast, the amount of cholesterol efflux from SR-BI CHO cells into HDL was almost the same between the two HDLs. Therefore, when CE-rich HDL was added to the medium of SR-BI CHO cells, the intracellular CE content increased significantly. Moreover, the particle size of HDL in CETP-deficient patient decreased significantly when the HDL was added to the medium of SR-BI CHO cells, and this HDL showed an increment of CE efflux from foam cells. These results indicate that SR-BI reduces the cholesterol content and size of the CE-rich HDL from CETP deficiency, which ultimately activate reverse cholesterol transport system.

Synergically increased expression of CD36, CLA-1 and CD68, but not of SR-A and LOX-1, with the progression to foam cells from macrophages.

Several species of scavenger receptors have so far been identified. However, it remains unclear which receptors are more crucial for the foam cell formation and progression. In the present study, we compared five major scavenger receptors (SR-A, CD36, CLA-1, CD68, and LOX-1) in their levels of expression at the different stages of foam cells derived from THP-1 cells. The expression of all scavenger receptors examined was up-regulated by the stimulation with TPA for 48 hours, despite the expressions of SR-A, CD36 and LOX-1 being very low before the treatment with TPA. Four to 7 days after the removal of TPA, the levels of CD36, CLA-1 and CD68 were increased significantly. In contrast, the expression of SR-A was suppressed significantly, and no change was observed in that of LOX-1. Furthermore, when the transformed macrophages were incubated with oxidized LDL, in which the uptake of [3H] cholesteryl oleoyl ether-labeled OxLDL was linear up to 7 days after the addition of OxLDL, the expression of CD36, CLA-1 and CD68 were greatly enhanced. This enhancement was more prominent than that without oxidized LDL, and the enhancement was sustained throughout the experimental period. On the other hand, SR-A was not up-regulated, and LOX-1 was down-regulated. We thus propose that CD36, CLA-1 and CD68, but not SR-A and LOX-1, may play crucial roles in the progression of macrophages to foam cells, which is a key step for the initiation of atherosclerosis.