Design and synthesis of unique morphinan-type molecules: Their application to the search for the unexplored binding domain between opioid receptors and morphinan ligands.

The morphinan skeleton is valued in drug discovery for its beneficial physicochemical properties and is recognized as a crucial template for opioid receptor ligands. In morphinan derivatives, it is well-established that the nitrogen atom within the piperidine ring (D-ring) interacts with the amino acid residues of the opioid receptors. This interaction is recognized as one of the crucial pharmacophores between the morphinan molecule and the opioid receptors. Consequently, the structure-activity relationships (SAR) surrounding the D-ring are not well-studied, due to concerns that structural transformations around the nitrogen at the 17-position could disrupt this interaction. In this study, we found that our novel morphinan-type ligands with a side chain containing a heteroatom positioned above the d-ring have binding affinity for the opioid receptors. These novel skeletons could provide unique templates with the desired side chain above the D-ring in the morphinan skeleton, and thus, potentially advance the SAR studies of morphinan ligands with the opioid receptors.

Unexpected Rearrangement Reactions of the 14-Aminonaltrexone Skeleton.

The reaction of 14-aminonaltrexone with acetic anhydride was found to produce a range of different novel compounds between the free compound and its hydrochloride. The hydrochloride produced a compound with an acetylacetone moiety, whereas the free form produced a compound with a pyranopyridine moiety. Efforts to isolate reaction intermediates and density functional theory calculations have elucidated those formation mechanisms with both bearing the novel morphinan-type skeleton. Furthermore, a derivative with the acetylacetone moiety showed binding to opioid receptors.

[The Usefulness of a Pamphlet for Preventing Exposure to Antineoplastic Agents at Cancer Patients' Homes and an Awareness Survey for Pharmacists about Providing Information to Cancer Patients about Exposure to Antineoplastic Agents].

As the number of patients undergoing outpatient chemotherapy has increased, there is concern that cancer patients' family members are unknowingly exposed to antineoplastic agents at home through cancer patients' excrement or other secreted materials. In this study, we created a pamphlet that introduces several methods to prevent exposure to antineoplastic agents at home and conducted a questionnaire survey to assess the usefulness of the pamphlet. The results indicated that more than 90% of patients believed that the pamphlet was "useful" or "very useful" for ensuring safety with respect to antineoplastic agents at home. Further, most patients responded that the pamphlet decreased their anxieties about their disease and/or treatment. In order to examine pharmacists' involvement in providing information to cancer patients about exposure to antineoplastic agents, we conducted another questionnaire survey, with pharmacists working at Sapporo-Higashi Tokushukai Hospital and Sapporo Tokushukai Hospital. The results indicated that 41 out of 46 pharmacists practiced medication counseling; however, 39 pharmacists did not provide patients with instructions on ways to prevent exposure to antineoplastic agents at home. Their primary reason was a lack of adequate information to do so. Accordingly, the pamphlet prepared in our study would be an effective way to provide guidance for preventing exposure to antineoplastic agents at home.

Daily Intake of Heat-killed Lactobacillus plantarum L-137 Decreases the Probing Depth in Patients Undergoing Supportive Periodontal Therapy.

PURPOSE: Heat-killed Lactobacillus plantarum L-137 (HK L-137) has been shown to activate innate and acquired immunity in humans. The aim of this randomised, double-blind, placebo-controlled clinical trial was to examine the effects of the oral administration of HK L-137 on the outcome of periodontal therapy. MATERIALS AND METHODS: Thirty-nine patients undergoing supportive periodontal therapy (SPT) were randomly assigned to receive a capsule containing 10 mg of HK L-137 or a placebo capsule daily for 12 weeks. Nineteen patients in the experimental group and 17 patients in the control group were followed-up. Clinical parameters, including plaque index (PI), gingival index (GI), bleeding on probing (BOP), and probing depth (PD) were scored at baseline and weeks 4, 8 and 12 prior to prophylaxis in conjunction with regular SPT visits. RESULTS: BOP and the number of teeth or sites with PD ≥ 4 mm were significantly reduced in both groups by a successive SPT programme, while there was significantly greater PD reduction (p < 0.05) at teeth with site(s) with PD ≥ 4 mm at baseline in the experimental group than in the control group at week 12. CONCLUSION: These clinical findings suggest that daily HK L-137 intake can decrease the depth of periodontal pockets in patients undergoing supportive periodontal therapy.