We examined whether water-hydroxyapatite (HAP) images improve the diagnostic accuracy of bone metastasis compared with non-contrast CT alone. We retrospectively evaluated dual-energy computed tomography (DECT) images of 83 cancer patients (bone metastasis, 31; without bone metastasis, 52) from May 2018 to June 2019. Initially, two evaluators examined for bone metastasis on conventional CT images. In the second session, both CT and CT images plus water-HAP images on DECT. The confidence of bone metastasis was scored from 1 (benign) to 5 (malignant). The sensitivity, specificity, positive predictive values, and negative predictive values for both modalities were calculated based on true positive and negative findings. The intra-observer area under curve (AUC) for detecting bone metastasis was compared by receiver operating characteristic analysis. Kappa coefficient calculated the inter-observer agreement. In conventional CT images, sensitivity, specificity, positive predictive value, and negative predictive value of raters 1 and 2 for the identification of bone metastases were 0.742 and 0.710, 0.981 and 0.981, 0.958 and 0.957, and 0.864 and 0.850, respectively. In water-HAP, they were 1.00 and 1.00, 0.981 and 1.00, 0.969 and 1.00, and 1.00 and 1.00, respectively. In CT, AUCs were 0.861 and 0.845 in each observer. On water-HAP images, AUCs were 0.990 and 1.00. Kappa coefficient was 0.964 for CT and 0.976 for water-HAP images. The combination of CT and water-HAP images significantly increased diagnostic accuracy for detecting bone metastasis. Water-HAP images on DECT may enable accurate initial staging, reduced radiation exposure, and cost.
M 1 and/or M 4 muscarinic acetylcholine receptors are suggested to be involved in the pathogenesis and treatment of schizophrenia. To validate the antipsychotic potential of M 4 receptor activation, we evaluated the antipsychotic properties of the selective M 4 agonist (Compound 1, Bioorg. Med. Chem. Lett., 24, 2909Lett., 24, , 2014 in mice and compared them to those of xanomeline (M 1 /M 4 preferring agonist). Apomorphine (APO, 4 mg/kg, s.c.)-induced hyperactivity test was used for the evaluation of antipsychotic activity and pole-test for the assessment of extrapyramidal side effects (bradykinesia). Treatment of animals with Compound 1 (0.3-3 mg/kg, s.c.) significantly inhibited APO-induced hyperactivity in a dose-dependent manner. Compound 1 did not induce bradykinesia at higher doses (1-10 mg/kg, s.c.), and it rather tended to reduce haloperidol (1 mg/kg, i.p.)-induced bradykinesia. Meanwhile, xanomeline (1-10 mg/kg, s.c.) also inhibited APO-induced hyperactivity, but it was 3 times less potent than Compound 1. In addition, xanomeline induced bradykinesia at 3-10 mg/kg and muscle relaxation at 10-30 mg/kg (s.c.). Our results suggest that activation of M 4 receptors is linked to the antipsychotic activity and is more promising than the mixed M 1 /M 4 receptor activation.
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