Adiponectin-Receptor Agonistic Dipeptide Tyr-Pro Stimulates the Acetylcholine Nervous System in NE-4C Cells.

The dipeptide Tyr-Pro has physiological potential for intact transportability into the brain parenchyma, prevention of cognitive impairment, and an adiponectin receptor 1 (AdipoR1) agonistic effect. The present study aimed to understand the effect of Tyr-Pro on the acetylcholine (ACh) nervous system and its underlying mechanism in NE-4C nerve cells. Concentration-dependent ACh production was induced by stimulation with Tyr-Pro and AdipoRon (an AdipoR1 agonist), along with the expression of AdipoR1 and choline acetyltransferase (ChAT) in NE-4C cells. By knocking down AdipoR1 in the cells, Tyr-Pro promoted ChAT expression, along with the activations of AMPK and ERK 1/2. Tyr-Pro did not alter acetylcholinesterase or ACh receptors, indicating that the dipeptide might operate as an ACh accelerator in nerve cells. This study provides the first evidence that the AdipoR1 agonistic Tyr-Pro is a promising dipeptide responsible for the stimulation of the ACh nervous system by AdipoR1-induced ChAT activation.

Impact of osteoporosis liaison services on the expected lifetime osteoporosis-related medical expenses of patients with fragility fracture in a private hospital in Japan.

We report the efficacy of a Japanese fracture liaison service (FLS), the osteoporosis liaison service (OLS), in suppressing osteoporosis-related expenses from the public insurance by preventing secondary fracture in spite of higher medication costs during expected life spans. OLS could reduce medical expenses for osteoporosis in all age groups. PURPOSE: Osteoporosis liaison services (OLS), which are based on fracture liaison services (FLS), are used in Japan to prevent both primary and secondary fractures in older people. We aimed to clarify the effects of OLS on the medical expenses. PATIENTS AND METHODS: We compared patients with fragile fractures hospitalized to Saitama Jikei Hospital before and after implementing OLS. These were labeled a non-OLS group and an OLS group, and they were further organized by age (< 75, 75-84, and ≥ 85 years). The expected osteoporosis-related medical expenses during life were calculated by the occurrence, fracture site, medication, and life expectancy and compared between the non-OLS and OLS groups by the age group. RESULTS: The non-OLS group included 400 people (100 males and 300 females, mean age 81.7 ± 9.7 years), comprising 154 with vertebral fractures and 246 with hip fractures. The OLS group included 406 patients (101 males and 305 females, mean age 82.4 ± 9.3 years), of whom 161 had vertebral fractures and 245 had hip fractures. The suppressive secondary fracture effects of OLS were previously reported. The expected expense of osteoporosis treatment in the OLS group was found to be greater than that in the non-OLS group for all age groups. In contrast, expected expenses for treating secondary fractures were shown to increase more in the non-OLS group. However, total expenses were lower in the OLS group across all age groups. CONCLUSION: The implementation of OLS can reduce overall healthcare costs despite the increased expenses required to provide medical therapy and periodic examinations.

Effectiveness of a Japanese multi-professional cooperative osteoporosis liaison service at a private hospital for decreasing secondary fractures in osteoporosis patients with fragility fractures.

PURPOSE: A fracture liaison service (FLS) was established in England to support patients with fragility fractures, and it was introduced in Japan as the osteoporosis liaison service (OLS). The study aim was to determine if the Japanese OLS/FLS prevents secondary fractures in patients with fragility fractures and assess the value of the OLS/FLS. Our OLS/FLS evaluated the status of osteoporosis in patients and their life circumstances. Additionally, it introduced osteoporosis therapies during the patients' hospitalization period and then continued periodical examinations and prescription of drug after discharge. PATIENTS AND METHODS: This study was conducted in consecutive patients: 400 were assigned to the non-OLS group and 406 to the OLS group. The mean age of the patients was 81.7 ± 9.7 years in the non-OLS group (154 patients with vertebral fractures and 246 with hip fractures; 100 males, 300 females) and 82.4 ± 9.3 years in the OLS group (245 patients with hip fractures and 161 with vertebral fractures; 101 males, 305 females). RESULTS: During hospitalization, 74.9% of the OLS group patients started medications and 63.9% of patients continued after discharge, while 35.8% and 53.5% of non-OLS group. The incidence rate of secondary fractures was 89.8/1000 person-years in the non-OLS group, and 55.2/1000 person-years in the OLS group. The multivariate Cox hazards test showed that secondary fractures after vertebral or hip fractures increased with age, and the risk was 0.58-fold in patients in the OLS group. CONCLUSION: OLS was effective in reducing secondary fractures in patients with osteoporosis with fragility fractures.