Changes in chronic disease medications after admission to a Geriatric Health Services Facility: A multi-center prospective cohort study.

Older adults often receive polypharmacy, including some medications for chronic diseases. Nutritional management after admission to a nursing home may enable to deprescribe some chronic disease medications. This study aimed to investigate the status of deprescribing of chronic disease medications among nursing home residents, and to assess the appropriateness based on changes of laboratory test values and nutritional status. A multi-center prospective cohort study was conducted in 6 Geriatric Health Services Facilities, a major type of nursing homes in Japan. Newly admitted residents aged ≥ 65 years who took ≥1 medication for hypertension, diabetes, or dyslipidemia at admission were recruited. Participants who stayed for 3 months were included in the analysis. Medications at admission and 3 months after admission and situations for deprescribing were investigated. Changes in body mass index, blood pressure, laboratory tests (e.g., cholesterol and hemoglobin A1c levels), energy intake, and International Classification of Functioning, Disability and Health staging were evaluated. Sixty-nine participants (68% female, 62% aged ≥ 85 years) were included. At admission, 60 participants had medications for hypertension, 29 for dyslipidemia, and 13 for diabetes. Those receiving lipid-modifying drugs (mainly statins) decreased from 29 to 21 (72%; P = .008), since their cholesterol levels was within the normal range or was low at admission, and they had no history of cardiovascular events. However, there were no statistically significant changes in the frequencies of antihypertensive drugs (60 to 55; 92%; P = .063) or antidiabetic drugs (13 to 12; 92%; P = 1.000). During the 3-month observation, body mass index and diastolic blood pressure decreased, while energy intake and serum albumin level increased. Nutritional management after admission to a ROKEN may facilitate appropriate deprescribing of lipid-modifying drugs, by offseting the effects of discontinuation of these drugs.

Targeting Podoplanin for the Treatment of Osteosarcoma.

PURPOSE: Osteosarcoma, the most common bone malignancy in children, has a poor prognosis, especially when the tumor metastasizes to the lungs. Therefore, novel therapeutic strategies targeting both proliferation and metastasis of osteosarcoma are required. Podoplanin (PDPN) is expressed by various tumors and is associated with tumor-induced platelet activation via its interaction with C-type lectin-like receptor 2 (CLEC-2) on platelets. We previously found that PDPN contributed to osteosarcoma growth and metastasis through platelet activation; thus, in this study, we developed an anti-PDPN humanized antibody and evaluated its effect on osteosarcoma growth and metastasis. EXPERIMENTAL DESIGN: Nine osteosarcoma cell lines and two osteosarcoma patient-derived cells were collected, and we evaluated the efficacy of the anti-DPN-neutralizing antibody PG4D2 and the humanized anti-PDPN antibody AP201, which had IgG4 framework region. The antitumor and antimetastasis effect of PG4D2 and AP201 were examined in vitro and in vivo. In addition, growth signaling by the interaction between PDPN and CLEC-2 was analyzed using phospho-RTK (receptor tyrosine kinase) array, growth assay, or immunoblot analysis under the supression of RTKs by knockout and inhibitor treatment. RESULTS: We observed that PG4D2 treatment significantly suppressed tumor growth and pulmonary metastasis in osteosarcoma xenograft models highly expressing PDPN. The contribution of PDGFR activation by activated platelet releasates to osteosarcoma cell proliferation was confirmed, and the humanized antibody, AP201, suppressed in vivo osteosarcoma growth and metastasis without significant adverse events. CONCLUSIONS: Targeting PDPN with a neutralizing antibody against PDPN-CLEC-2 without antibody-dependent cell-mediated cytotoxicity and complement-dependent cytotoxicity is a novel therapeutic strategy for PDPN-positive osteosarcoma.

Functional role of the Tau protein in epithelial ovarian cancer cells.

Aim: The microtubule-associated Tau protein is a marker of paclitaxel sensitivity in ovarian cancer. The aim of the present study was to elucidate the function of the Tau protein in epithelial ovarian cancer. Methods: The correlation between Tau protein expression and the response to paclitaxel by using several ovarian cancer cell lines was investigated. Results: A Western blot showed that the expression level of the Tau protein was the highest in the TOV112D cells. A cell-counting kit showed that the proliferation rates were more inhibited in the cells with down-regulated Tau protein than in the control cells, both with and without paclitaxel treatment. The proliferation rates of the control cells and the TOV112D cells also were compared with Tau protein overexpression. The level of cell proliferation was more inhibited in the cells that overexpressed the Tau protein, compared to the control cells, both with and without paclitaxel treatment. It was shown that both the down-regulation and the overexpression of the Tau protein were related to the inhibition of TOV112D cell proliferation. Early and late apoptosis of the TOV112D cells that were transfected with Tau cDNA plasmid construct or Tau small interfering RNA significantly increased. Conclusion: These findings suggest that the molecular targeting of the Tau protein could be a potential treatment for ovarian cancer.

Differences in the sensitivity of ovarian cancer to photodynamic therapy and the mechanisms for those differences.

Protoporphyrin IX (PpIX) levels are crucial to the antitumor action of photodynamic therapy (PDT). In the present study, the underling molecular mechanisms for the variation in PpIX levels in ovarian cancer cells were investigated. Five ovarian cancer cell lines were subcutaneously grafted onto the backs of nude mice. Once tumors had developed, 5-aminolevulinic acid methyl ester hydrochloride (methyl-ALA) was administered intraperitoneally and the tumor was irradiated twice/week. PpIX levels in the tumor were assayed using high-performance liquid chromatography. Enzymes involved in heme synthesis and degradation were screened using a microarray technique. Expression of the glutathione transferase Omega-1 (GSTO1) gene involved in the conversion of PpIX into heme in cells was quantified using the reverse transcription-quantitative polymerase chain reaction. In HTOA, HRA and DISS cells, PDT resulted in significant tumor shrinkage in comparison with the controls. In MCAS and TOV21G cells, no significant alterations in tumor growth were identified compared with the untreated cells. PpIX levels increased significantly in HTOA, DISS and HRA cells compared with in MCAS and TOV21G cells. A comparison of genetic profiles using PDT-sensitive DISS cells and PDT-resistant MCAS cells indicated that MCAS cells exhibited significantly increased levels of δ-aminolevulinate synthase (a rate-limiting enzyme in heme synthesis), heme oxygenase 2 (an enzyme that degrades heme into biliverdin), and biliverdin reductase B (an enzyme that reduces biliverdin into bilirubin) in comparison with DISS cells. The level of GSTO1 expression in HTOA, HRA and DISS cells was ~2.5-fold that in MCAS and TOV21G cells. Sensitivity to PDT is related to PpIX levels in cells. The results of the present study suggested that PpIX tends not to accumulate in PDT-resistant cells despite active heme synthesis and degradation, and that high levels of GSTO1 expression are associated with increased sensitivity to PDT.

Laparoscopically assisted cervical canalization and neovaginoplasty in a woman with cervical atresia and vaginal aplasia.

Cervical atresia is a Müllerian duct system anomaly, and it is often associated with vaginal aplasia. We report the case of a 17-year-old girl who presented with primary amenorrhea and cyclical abdominal pain, and was diagnosed with cervical atresia and vaginal aplasia that were treated laparoscopically. Laparoscopically assisted cervical canalization and neovaginoplasty were performed to relieve dysmenorrhea and allow for sexual intercourse and fertility. We did not use a bowel segment, skin, or peritoneum as a graft for the neovaginoplasty. To prevent adhesions and promote epithelialization, we used an estrogen-containing cream. Moreover, we did not use a vaginal mold. The patient is free of cervical stenosis and able to have intercourse. Long-term follow-up is necessary to ensure a future pregnancy and childbirth.

A case of bilateral tubal pregnancy.

Bilateral tubal pregnancy is very rare and occurs in only 1 out of every 200,000 spontaneous pregnancies. In this case, a 29-year-old woman with a history of primary infertility underwent treatment with human menopausal gonadotropin (hMG)-human chorionic gonadotropin (hCG), and became pregnant. A gestational sac (GS) was not detected in the uterus and transvaginal ultrasonography (USG) revealed GS with fetal heartbeat in the left adnexa at 7 weeks and 6 days of gestation. The patient underwent laparoscopic surgery and ultimately, bilateral tubal pregnancy was diagnosed. Consequently, bilateral fallopian tube resection was performed. Afterwards, she conceived by assisted reproductive technology (ART) and delivered vaginally. This case suggests that even if a GS is found in one fallopian tube by USG, it is important to evaluate the other fallopian tube carefully. Abbreviations: TV-USG, transvaginal ultrasound; hCG, human chorionic gonadotropin; DD, dichorionic-diamniotic.

A Strategy Using Photodynamic Therapy and Clofibric Acid to Treat Peritoneal Dissemination of Ovarian Cancer.

BACKGROUND: The current study examined the effectiveness of concurrent therapy using photodynamic therapy (PDT) and clofibric acid (CA) to treat peritoneal carcinomatosis resulting from ovarian cancer. MATERIALS AND METHODS: Nude rats were used to create a model of peritoneal carcinomatosis resulting from ovarian cancer and the effectiveness of PDT with 5-aminolevulinic acid methyl ester hydrochloride (methyl-ALA-PDT) was determined. The survival time of rats receiving that therapy was compared to the survival time of a control group. Rats with peritoneal carcinomatosis resulting from ovarian cancer were divided into 3 groups: a group that received debulking surgery (DS) alone, a group that received DS+methyl-ALA-PDT, and a group that received DS+methyl-ALA-PDT+CA. The survival time of the 3 groups was compared. Protoporphyrin, a metabolite of methyl-ALA, produces a photochemical action when activated by light. The level of protoporphyrin (the concentration) that reached organs in the abdomen was measured with HPLC. RESULTS: Rats receiving methyl- ALA-PDT had a significantly longer survival time compared to the controls. Rats with peritoneal carcinomatosis that received DS+methyl-ALA-PDT+CA had a significantly longer survival time compared to the rats that received DS alone. Some of the rats that received concurrent therapy survived for a prolonged period. Protoporphyrin was highly concentrated in peritoneal metastases, but only small amounts reached major organs in the abdomen. PDT was not found to result in necrosis in the intestines. CONCLUSIONS: The results indicated that concurrent therapy consisting of PDT with methyl-ALA and CA is effective at treating peritoneal carcinomatosis resulting from ovarian cancer without damaging organs.

A case of small cell carcinoma of the vagina.

Primary small cell carcinoma of the vagina is quite rare, and a standard treatment has not been established yet. Herein, we report a case of an 81-year-old woman who was diagnosed with a vaginal tumor without continuity with the uterine cervix. Histopathological diagnosis indicated alveolar solid growth of nuclear chromatin-rich atypical cells with a high N/C ratio and a partially recognized rosette-like structure, suggesting a differentiated neuroendocrine system. Chromogranin A and synaptophysin were positive. Stage I vaginal small cell carcinoma localized to the vagina was diagnosed. The tumor disappeared by radiation monotherapy with external beam irradiation and endocavitary irradiation. The patient remains alive without any disease 1 year and 8 months after the treatment, suggesting the efficacy of radiotherapy in small cell carcinoma of the vagina.

Analysis of antioxidant activities contained in the Boesenbergia pandurata Schult. Rhizome.

The rhizome of Boesenbergia pandurata Schult. was found to possess potent antioxidant activity in a rat brain homogenate model. Bioassay-guided isolation of the active compounds from a CH2Cl2-MeOH (1:1) extract led to the isolation of 5-hydroxy-7-methoxyflavanone, panduratin A, 5,7-dihydroxyflavanone, 2',6'-dihydroxy-4'-methoxychalcone, 2',4'-dihydroxy-6'-methoxychalcone, and 4-hydroxypanduratin A. Panduratin A, 4-hydroxypanduratin A, and 2',6'-dihydroxy-4'-methoxychalcone were also found to exert neuroprotective effects.

Heart rate variability with repetitive exposure to music.

Previous studies of physiological responses to music showed inconsistent results, which might be attributable to methodological differences. Heart rate variability has been used to assess activation of the sympathetic and the parasympathetic nervous systems. The present study aimed to examine heart rate variability with repetitive exposure to sedative or excitative music. The participants were 13 undergraduate or graduate students who were each exposed to three conditions sedative music (SM), excitative music (EM), and no music (NM) on different days. Each participant underwent four sessions of one condition in a day. Sedative music and no music each induced both high relaxation and low tension subjectively. However, excitative music decreased perceived tension and increased perceived relaxation as the number of sessions increased. The low-frequency (LF) component of heart rate variability (HRV) and the LF/HF (high-frequency) ratio increased during SM and EM sessions but decreased during NM sessions. The HF component of HRV during SM was higher than that during EM but the same as that during NM. These findings suggest that excitative music decreased the activation of the parasympathetic nervous system.