The needs of patients with noncancer diseases and their families from hospital-based specialized palliative care teams in Japan.

BACKGROUND: Hospital-based specialized palliative care teams (HSPC) are important for symptom management and ethics support, especially during complex decision-making, but the needs of patients with noncancer diseases and their families from the HSPC are unclear. This study aimed to (I) compare the prevalence of symptom between patients with and without cancer and explore changes in symptom intensity after HSPC consultation in patients with noncancer; (II) determine factors related to ethics support; and (III) compare the percentage of request contents from patients and their families when a certified nurse specialist in gerontological nursing (geriatric care nurse below) is present in the HSPC to that when a certified nurse specialist in palliative care (palliative care nurse below) is present in the HSPC. METHODS: We utilized a retrospective cohort study to analyze 761 patients (360 with noncancer and 401 with cancer) referred to our HSPC at the National Center for Geriatrics and Gerontology using 10-year data (since 2011) available in an electronic medical record database. (I) Symptom scores of the Support Team Assessment Schedule were compared between noncancer and cancer groups and between initial and 1-week assessments for noncancer patients. (II) Ethics support was compared between noncancer (including dementia) and cancer. The presence or absence of ethics support requests, which was set as the objective variable, was examined using logistic regression analysis. (III) The percentage of request contents selected from nine items defaulted on the electronic medical record when a geriatric care nurse was present in our HSPC were compared to those when a palliative care nurse was present in our HSPC. RESULTS: Compared to those with cancer, patients with noncancer suffered more from dyspnea and sputum accumulation. More than 10% of patients with noncancer had suffered from pain, dyspnea, sputum accumulation, and anorexia that required treatment, with symptom scores showing improvement after 1 week of HSPC involvement, except for the sputum accumulation. Moreover, for anorexia, symptom scores improved, but >10% of these patients continued to suffer. Patients with noncancer diseases, including dementia, received ethics support than those with cancer without dementia. More requests for ethics support were received when a geriatric care nurse was in the HSPC than when a palliative care nurse was in the HSPC. Logistic regression analysis revealed that requests for ethics support were more frequent from patients or families with impaired decision-making capacity or when the patient lacked an advocate. CONCLUSIONS: The needs of patients with noncancer diseases and families from the HSPC in Japan included (I) symptom management for intractable conditions, such as sputum accumulation; (II) ethics support for patients with noncancer diseases, including dementia, with impaired decision-making capacity, and without advocates; and (III) advice on ethics issues from a geriatric care nurse.

Diet-induced inflammation is associated with sarcopenia and muscle strength in older adults who visit a frailty clinic.

BACKGROUND: Diet-induced inflammation may be associated with sarcopenia; however, few reports have examined this relationship. AIM: To examine the association between the dietary inflammatory index (DII) and sarcopenia in older adults who visited a frailty clinic in Japan. METHODS: This cross-sectional study used outpatient data from the Frailty Registry Study. The DII is an index of diet-induced inflammation, and a dietary assessment was performed using a brief self-administered diet history questionnaire to calculate the DII score. We classified DII scores by quartiles (Q1-Q4), and sarcopenia was diagnosed according to the Asian Working Group for Sarcopenia 2019 consensus. Logistic regression analyses for sarcopenia were performed. Age, sex, comorbidities, and physical activity were entered as confounding factors (Model 1) and Models 2, 3, and 4 with BMI, protein intake, and energy intake added to Model 1. RESULTS: We included 304 patients in the analysis (mean age, 77.6 ± 6.3 years; female, 67.4%). The prevalence of sarcopenia was 14.5%. Logistic regression analyses showed that DII scores were significantly associated with sarcopenia in Model 1 and 2 (Model 1, reference: Q1, Q4: OR 3.10, P = 0.020; Model 2, Q4: OR 3.40, P = 0,022) but not in Model 3 and 4. DISCUSSION: Diet-induced inflammation is associated with a higher likelihood of sarcopenia; however, this association disappeared after confounding for protein and energy intake. CONCLUSIONS: The results demonstrated that dietary protein and energy parameters were the main drivers for muscle health in medical patients.

Unbiased profiling of volatile organic compounds in the headspace of Allium plants using an in-tube extraction device.

BACKGROUND: Plants produce and emit important volatile organic compounds (VOCs), which have an essential role in biotic and abiotic stress responses and in plant-plant and plant-insect interactions. In order to study the bouquets from plants qualitatively and quantitatively, a comprehensive, analytical method yielding reproducible results is required. RESULTS: We applied in-tube extraction (ITEX) and solid-phase microextraction (SPME) for studying the emissions of Allium plants. The collected HS samples were analyzed by gas chromatography-time-of-flight-mass spectrometry (GC-TOF-MS), and the results were subjected to multivariate analysis. In case of ITEX-method Allium cultivars released more than 300 VOCs, out of which we provisionally identified 50 volatiles. We also used the VOC profiles of Allium samples to discriminate among groups of A. fistulosum, A. chinense (rakkyo), and A. tuberosum (Oriental garlic). As we found 12 metabolite peaks including dipropyl disulphide with significant changes in A. chinense and A. tuberosum when compared to the control cultivar, these metabolite peaks can be used for chemotaxonomic classification of A. chinense, tuberosum, and A. fistulosum. CONCLUSIONS: Compared to SPME-method our ITEX-based VOC profiling technique contributes to automatic and reproducible analyses. Hence, it can be applied to high-throughput analyses such as metabolite profiling.

Role of PGE2 in the colonic motility: PGE2 generates and enhances spontaneous contractions of longitudinal smooth muscle in the rat colon.

The aim of this study was to determine which PGE2 receptors (EP1-4 receptors) influence colonic motility. Mucosa-free longitudinal smooth muscle strips of the rat middle colon spontaneously induced frequent phasic contractions (giant contractions, GCs) in vitro, and the GCs were almost completely abolished by a cyclooxygenase inhibitor, piroxicam, and by an EP3 receptor antagonist, ONO-AE3-240, but enhanced by tetrodotoxin (TTX). In the presence of piroxicam, exogenous PGE2, both ONO-AE-248 (EP3 agonist), and ONO-DI-004 (EP1 agonist) induced GC-like contractions, and increased the frequency and amplitude. These effects of EP receptor agonists were insensitive to TTX and ω-conotoxins. In immunohistochemistry, the EP1 and EP3 receptors were expressed in the longitudinal smooth muscle cells. These results suggest that the endogenous PGE2 spontaneously generates and enhances the frequent phasic contractions directly activating the EP1 and EP3 receptors expressed on longitudinal smooth muscle cells in the rat middle colon.

Development of a Direct Headspace Collection Method from Arabidopsis Seedlings Using HS-SPME-GC-TOF-MS Analysis.

Plants produce various volatile organic compounds (VOCs), which are thought to be a crucial factor in their interactions with harmful insects, plants and animals. Composition of VOCs may differ when plants are grown under different nutrient conditions, i.e., macronutrient-deficient conditions. However, in plants, relationships between macronutrient assimilation and VOC composition remain unclear. In order to identify the kinds of VOCs that can be emitted when plants are grown under various environmental conditions, we established a conventional method for VOC profiling in Arabidopsis thaliana (Arabidopsis) involving headspace-solid-phase microextraction-gas chromatography-time-of-flight-mass spectrometry (HS-SPME-GC-TOF-MS). We grew Arabidopsis seedlings in an HS vial to directly perform HS analysis. To maximize the analytical performance of VOCs, we optimized the extraction method and the analytical conditions of HP-SPME-GC-TOF-MS. Using the optimized method, we conducted VOC profiling of Arabidopsis seedlings, which were grown under two different nutrition conditions, nutrition-rich and nutrition-deficient conditions. The VOC profiles clearly showed a distinct pattern with respect to each condition. This study suggests that HS-SPME-GC-TOF-MS analysis has immense potential to detect changes in the levels of VOCs in not only Arabidopsis, but other plants grown under various environmental conditions.

Adiponectin does not bind to gelatin: a new and easy way to purify high-molecular-weight adiponectin from human plasma.

Human plasma contains three forms of adiponectin, a trimer, a hexamer, and a high-molecular-weight (HMW) multimer. We previously reported HMW adiponectin was a gelatin-binding protein of 28 kDa (GBP28), it having been purified due to its affinity to gelatin-Cellulofine (Nakano, Y., et al. Isolation and characterization of GBP28, a novel gelatin-binding protein purified from human plasma. J. Biochem. 1996. 120: 803-12). Although HMW adiponectin binds to gelatin-Cellulofine, it cannot bind to gelatin-Sepharose. Gelatin-Cellulofine was made of formyl-Cellulofine and gelatin, and we found that HMW adiponectin binds to reduced formyl-Cellulofine with similar affinity as to gelatin-Cellulofine. Through only two steps using reduced formyl-Cellulofine and DEAE-Sepharose, HMW adiponectin can be effectively purified from human plasma.

Endocrinological properties of two novel nonsteroidal progesterone receptor modulators, CP8816 and CP8863.

We have isolated PF1092A, B, and C, novel nonsteroidal progesterone ligands with preferential affinity for the progesterone receptor, from fermentation broth of a fungus [Tabata Y, Miike N, Hatsu M, Kurata Y, Yaguchi T, Someya A, Miyadoh S, Hoshiko S, Tsuruoka T, and Omoto S (1997) J Antibiot 50:304-308; Tabata Y, Hatsu M, Kurata Y, Miyajima K, Tani M, Sasaki T, Kodama Y, Tsuruoka T, and Omoto S (1997) J Antibiot 50:309-313]. The original skeleton of PF1092, tetrahydronaphthofuranone, was modified synthetically to produce a new skeleton, tetrahydrobenzindrone, and in the present study, biological activities of two derivatives, CP8816 [(4aR,5R,6R,7R)-6-(N,N-dimethylaminocarbonyl)oxy-7-methoxy-4a,5,6,7-tetrahydro-1,3,4a,5-tetramethylbenz[f]indol-2(4H)-one] and CP8863 [(4aR,5R,6R,7R)-7-hydroxy-6-(N-methylcarbamoyl)oxy-4a,5,6,7-tetrahydro-1,3,4a,5-tetramethylbenz[f]indol-2(4H)-one], were investigated. Both CP8816 and CP8863 demonstrated selective binding to progesterone receptor and partial agonistic activity in a progesterone-dependent endogenous alkaline phosphatase expression assay. In the Clauberg-McPhail test, progestational activity of CP8816 (0.1 mg/kg s.c. or 10 mg/kg p.o.) was comparable to that of progesterone (0.15 mg/kg s.c.), and oral administration of CP8863 at more than 1.0 mg/kg also exerted similar effects. Anti-estrogenic (antiuterotropic) activity was confirmed on daily oral application of more than 0.1 mg/kg CP8863 for 3 days by inhibition of estrogen-dependent uterine wet weight gain in ovariectomized rats. CP8816 also exerted antiuterotropic activity at doses of 10 mg/kg (s.c.) and 100 mg/kg (p.o.). These results indicate that our nonsteroidal progesterone ligands have affinity for the progesterone receptor with partial progestational activity in vitro and clear progestational effects in vivo. Thus, these progesterone receptor modulator profiles suggest that CP8863 and CP8816 are good candidate compounds for treatment of hormone-dependent gynecological disorders.

CP8668, a novel orally active nonsteroidal progesterone receptor modulator with tetrahydrobenzindolone skeleton.

We investigated progestational activity of a new nonsteroidal compound, CP8668, ((4aR,5R,6R,7R)-7-methoxy-6-(N-propylaminocarbonyl)oxy-4a,5,6,7-tetrahydro-1,3,4a,5-tetramethylbenz[f]indol-2(4H)-one). CP8668 showed selective affinity for human progesterone receptor equal in strength to other steroidal progestins. CP8668 showed no significant affinity for human glucocorticoid receptor or human estrogen receptor and very weak affinity for rat androgen receptor. In endogenous and exogenous progesterone-dependent enzyme expression assays using human mammary carcinoma T47D, CP8668 showed mixed agonist-antagonist activity. However, in a rabbit endometrial transformation test, CP8668 showed good progestational activity following s.c. and p.o. administration. These results suggest that CP8668 is a selective and orally active progesterone receptor modulator, which shows mixed agonist-antagonist activity in in vitro transcription tests and agonist activity in endometrial transformation assays in rabbits, and that it is potentially a promising lead compound for a new type of orally active progesterone receptor modulator.

In vitro and in vivo characterization of novel nonsteroidal progesterone receptor antagonists derived from the fungal metabolite PF1092C.

We studied the pharmacological effects of novel nonsteroidal progesterone receptor antagonists CP8661 and CP8754, which were synthesized from the fungal metabolite PF1092C. CP8661 possess a tetrahydrobenzindolone skeleton and CP8754 possess a tetrahydronaphthofuranone skeleton. In binding assays for steroid receptors, CP8661 and CP8754 inhibited [(3)H]-progesterone binding to human progesterone receptors (hPR), though they are less potent than RU486. CP8661 also showed moderate affinity to rat androgen receptors (rAR), although CP8754 did not. Neither compound showed affinity to human glucocorticoid receptors (hGR) or human estrogen receptors (hER). In exogeneous and endogeneous PR-dependent enzyme expression assays using human mammary carcinoma T47D, CP8661 and CP8754 showed pure antagonistic activity. In a rabbit endometrial transformation test, CP8661 and CP8754 showed anti-progestational activity by s.c. administration in a dose-dependent manner; meanwhile, these compounds showed no progestational activity at the same dose. These results suggested that CP8661 and CP8754 are in vivo effective pure progesterone receptor antagonists and presented the possibility of synthesizing pure progesterone receptor antagonists from both tetrahydronaphthofuranone and tetrahydrobenzindolone skeletons.