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- Tarnow, Peter, 1963, et al.
(author)
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Postoperative analgesia by D-myo-inositol-1,2,6-trisphosphate in patients undergoing cholecystectomy.
- 1998
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In: Anesthesia and analgesia. - 0003-2999. ; 86:1, s. 107-10
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Journal article (peer-reviewed)abstract
- D-myo-inositol-1,2,6-trisphosphate (1,2,6-IP3) possesses antiinflammatory properties, such as reduced eicosanoid synthesis and inhibition of inflammation-induced edema. These properties suggest possible analgesic effects. The analgesic effect of 1,2,6-IP3 was evaluated in a double-blind, randomized study in 24 patients undergoing cholecystectomy. Ten patients received 1,2,6-IP3 as an intravenous (i.v.) bolus dose of 240 mg, followed by a continuous i.v. infusion at 90 mg/h for 24 h. The placebo group (n = 14) received corresponding volumes of isotonic saline. Postoperative pain (visual analog pain scale; VAS) and opiate analgesic requirements (ketobemidon) were evaluated during five postoperative days. Results showed significantly reduced pain during the first five postoperative days in patients treated with 1,2,6-IP3, as measured by using a VAS (P < 0.05). The requirements of opioid analgesics were significantly reduced during the first three postoperative days (P < 0.05). No drug-related side effects were observed. Results of the present study demonstrate a potent and long-lasting analgesic effect of 1,2,6-IP3, possibly related to its antiinflammatory properties. Implications: A new antiinflammatory drug under investigation, inositol-1,2,6-trisphosphate, was evaluated as a possible analgesic in a pilot study during the postoperative period in cholecystectomized patients. Results showed significantly lower pain assessment and opioid consumption, which should encourage further studies.
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- Thapper, Anders, et al.
(author)
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The Unperturbed Oxo-Sulfido Functional Group cis-Mo(VI)OS, Related to that in the Xanthine Oxidase Family of Molybdoenzymes: Synthesis, Structural Characterization and Reactivity Aspects
- 1999
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In: Inorganic Chemistry. - : American Chemical Society (ACS). - 1520-510X .- 0020-1669. ; 38:18, s. 4104-4114
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Journal article (peer-reviewed)abstract
- The oxo-sulfido functional group cis-MoVIOS is essential to the activity of the xanthine oxidase family of enzymes but has proven elusive to synthesis in molecules containing no other four-electron ligands. A direct route to molecules containing this group has been achieved. The reaction system [MoO2(OSiPh3)2]/L in dichloromethane yields the complexes [MoVIO2(OSiPh3)2L] (L = phen (1), Me4phen (2), 4,4'-Me2bpy (3), 5,5'-Me2bpy (4), 2 py (5)) (74-96%), which are shown to have a distorted octahedral structure of crystallographically imposed C2 symmetry (1, 5) with cis oxo and trans silyloxy ligands. The related reaction system [MoO3S]2-/2Ph3SiCl/L in acetonitrile affords the complexes [MoVIOS(OSiPh3)2L] (L = phen (6), Me4phen (7), 4,4'-Me2bpy (8), 5,5'-Me2bpy (9)) (36-69%). From the collective results of elemental analysis, mass spectrometry, 1H NMR, and X-ray structure determinations (6, 7), complexes 6-9 are shown to contain the cis-MoVIOS group in molecules with the same overall stereochemistry as dioxo complexes 1-5. The crystal structures of 6 and 7 exhibit O/S disorder, which was modeled in refinements with 50% site occupancies. The Mo=O (1.607(5) (6), 1.645(5) (7) Å) and Mo=S (2.257(3) (6), 2.203(2) (7) Å) bond distances obtained in this way are somewhat shorter and longer, respectively, than expected. Distances obtained by molybdenum EXAFS analysis using the GNXAS protocol for 6-9 (Mo=O 1.71-1.72 Å; Mo=S 2.18-2.19 Å) are considered more satisfactory and are in good agreement with EXAFS values for xanthine oxidase. Molybdenum K-edge data for 1 and 6-9 are reported. Reaction of 7 with Ph3P in dichloromethane results in sulfur abstraction and formation of [MoVOCl(OSiPh3)2(Me4phen)] (10), which has a distorted octahedral structure with cis O/Cl and cis silyloxy ligands. Sulfur rather than oxygen abstraction is favored by relative Mo=O/Mo=S bond strengths. Complexes 6-9 should allow exploration of the biologically significant cis-MoVIOS group.
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