Aluminum-26 and beryllium-10 in marine sediment.

Activities of aluminum-26 and beryllium-10 in marine sediment were measured at 0.01 +/- 0.13 and 4.4 +/- 0.9 disintegrations per minute, per kilogram dry weight, respectively. Only an upper limit of 0.03 could be determined for the ratio of aluminum-26 to beryllium-10 in the sediment. The ratio is probably explained by production by cosmic rays in the atmosphere.

Alendronate distributed on bone surfaces inhibits osteoclastic bone resorption in vitro and in experimental hypercalcemia models.

Alendronate is an aminobisphosphonate that acts as a potent inhibitor of osteoclastic bone resorption. To understand the mechanism of action of alendronate in vivo, in this study we investigated the relationship between distribution of [14C]-alendronate in rat bone and its effects on bone resorption in vitro or in rat hypercalcemic models. A single IV dose of 0.05 approximately 1.25 mg/kg inhibited the increase in plasma calcium level induced by bovine PTH or 1 alpha(OH)D3. The minimal effective dose of pamidronate (1.25 mg/kg) and etidronate (over 31.25 mg/kg) were at least 5 times and 25 times, respectively, higher than the dose of alendronate in the rat hypercalcemic model prepared by 1 alpha(OH)D3. The relative potencies of compounds in the hypercalcemic rat models reflected those of inhibitory effects on bone resorption in vitro. We conducted the ivory-slice assay under two conditions: (a) addition of a given bisphosphonate after adherence of the osteoclasts; and (b) preincubation of the ivory slices with a given bisphosphonate. The inhibitory IC50 values of alendronate under condition (b) were similar to those under condition (a). To evaluate the interaction between osteoclasts and alendronate in bone, we investigated the localization of [14C]-alendronate in the tibia of growing rats (4-day-old rats). Alendronate did not distribute uniformly in the tibia. At 1 day after injection (0.05 mg SC), dense labeling was seen primarily under osteoclasts. We injected 0.05 mg/kg of [14C]-alendronate (single i.v.) into rats [14C]-alendronate was rapidly eliminated from plasma, and mainly distributed to the bone in rats. These data suggest that alendronate which distributed on bone surface mainly contributed to the antihypercalcemic action in vivo.

Hypouricemic effect of the novel xanthine oxidase inhibitor, TEI-6720, in rodents.

We investigated the xanthine oxidase/xanthine dehydrogenase inhibitory activity and hypouricemic effect of a newly synthesized xanthine oxidase/xanthine dehydrogenase inhibitor, TEI-6720, 2-(3-cyano-4-isobutoxyphenyl)-4-methyl-5-thiazole-carboxylic acid, and compared its effects with those of allopurinol in rodents. TEI-6720 was found to inhibit bovine milk xanthine oxidase, and mouse liver and rat liver xanthine oxidase/xanthine dehydrogenase with IC50 values of 1.4, 1.8 and 2.2 nM, respectively. On bovine milk xanthine oxidase, TEI-6720 exhibited mixed-type inhibition and the Ki value was 0.7 nM. TEI-6720 displayed prolonged urate-lowering activity in normal mice and rats. We evaluated the hypouricemic effect of TEI-6720 on hyperuricemia induced by the uricase inhibitor, potassium oxonate (250 mg/kg s.c., 1 h before the test drugs), and measured the total molarity of both serum allantoin and urate in rats. Oral TEI-6720 and allopurinol had a hypouricemic effect 2 h after their administration to oxonate-pretreated rats with ED50 values of 1.5 and 5.0 mg/kg, respectively. Both compounds also reduced the combined molarity of uric acid and allantoin in rats. The ED50 values of TEI-6720 and allopurinol were 2.1 and 6.9 mg/kg p.o., respectively. These results suggest that TEI-6720 may be useful for the treatment of hyperuricemia.

Tacalcitol (1,24(OH)2D3, TV-02) inhibits phorbol ester-induced epidermal proliferation and cutaneous inflammation, and induces epidermal differentiation in mice.

In this study, we examined the cutaneous effects of tacalcitol [1,24(R)(OH)2D3] on epidermal proliferation, differentiation, and skin inflammation in vivo using hairless mice. Tacalcitol was shown to inhibit epidermal proliferation using TPA-induced ornithine decarboxylase activity and DNA synthesis as indices, and the induction of epidermal differentiation using type I transglutaminase activity as an index. Tacalcitol also displayed an antiinflammatory effect on TPA-induced inflammatory changes histopathologically. These results confirm the clinical efficacy of tacalcitol in psoriasis, and suggest that it may be efficacious in the treatment of other inflammatory skin diseases.

Antigenic variation of porcine transmissible gastroenteritis virus detected by monoclonal antibodies.

Mouse myeloma cells (SP2/O) were fused with spleen cells from BALB/c mice immunized with detergent-solubilized antigen of purified virus, and 21 monoclonal (MC) antibodies reactive in enzyme-linked immunosorbent assay with the TO-163 strain of porcine transmissible gastroenteritis (TGE) virus were obtained. Of these MC antibodies, 14, 6 and 1 were IgG1, IgG2a and IgM, respectively. All of the MC antibodies contained light chains of the kappa type. Of these MC antibodies, 8 were found to have neutralization (NT) activity against the TO-163 strain. Comparison of 7 strains of TGE virus by NT tests using our panel of MC antibodies confirmed their close antigenic relationships, but also revealed the occurrence of distinct antigenic differences. These results suggest that there may be at least 6 different epitopes involved in NT reaction on the virion of the TO-163 strain. This notion was confirmed by the competitive binding assay.

Detection of antibodies against porcine parvovirus in swine sera by enzyme-linked immunosorbent assay.

An enzyme-linked immunosorbent assay (ELISA) was developed for detection of antibody against porcine parvovirus in swine sera. The antigen used for the assay was partially-purified virus treated with fluorocarbon and shown to contain 7 proteins by sodium dodecylsulfate-polyacrylamide gel electrophoresis. Of these proteins 83-, 64- and 60-K proteins reacted in Western immunoblotting with swine serum after infection with porcine parvovirus. Antibody responses were demonstrated by ELISA in pigs subcutaneously-infected with porcine parvovirus as by hemagglutination-inhibition (HI) test and Western immunoblotting reaction with the 83-, 64- and 60-K viral proteins. The results of ELISA on random swine-serum samples were well-correlated with those of the HI test. These findings indicate the usefulness of the ELISA as a serological tool for porcine parvovirus infection.

Detection of antibodies against Akabane virus in bovine sera by enzyme-linked immunosorbent assay.

An enzyme-linked immunonosorbent assay was established for detection of antibodies to Akabane virus in bovine sera. The assay was shown to be a useful serological tool for studies on Akabane virus infection.

PK/PD and safety of a single dose of TMX-67 (febuxostat) in subjects with mild and moderate renal impairment.

A single oral dose of 20 mg febuxostat was administered to subjects with normal, mild or moderate impairment in renal function. There was less than a 2-fold difference in AUC of plasma unchanged febuxostat among the renal function groups, and changes in plasma urate levels from pre-dose levels were not significant. A total of five adverse events were reported with all mild in severity. The results indicate that renal impairment will have little clinical impact on the pharmacokinetics (PK), pharmacodynamics (PD) and safety of the study drug.

Pharmacokinetics and pharmacodynamics of febuxostat (TMX-67), a non-purine selective inhibitor of xanthine oxidase/xanthine dehydrogenase (NPSIXO) in patients with gout and/or hyperuricemia.

The diurnal change of sUA and the effect of febuxostat on this change were investigated in 10 patients with gout and/or hyperuricemia. The diurnal sUA change after the last dose during the 4-week treatment phase (20 mg, QD) was almost the same as the pre-treatment value. Considering the dose, the AUC(obs) and Cmax of unchanged drug in patients with gout and/or hyperuricemia were estimated to be similar to those of healthy male adults. The results show that a 6-week treatment with febuxostat is safe and well-tolerated in the target patient population for this drug.

[1,2-Diphenyl-N,N'-bis(salicylidene)-(RR,SS)-1,2-ethanediyldiaminato]nitridomanganese(V).

The title compound, [MnN(C(28)H(22)N(2)O(2))], has a distorted square-pyramidal coordination with an Mn[triple-bond]N bond length of 1.516 (2) A at the apical position. The five-membered chelate ring adopts a gauche conformation with the two phenyl groups in equatorial orientations.

The exo and endo isomers of [N,N'-bis(salicylidene)-1,2-diphenyl-(RS,SR)-1,2-ethanediyldiaminato]oxovanadium(IV).

The title complexes, exo- and endo-[VO(C(28)H(22)N(2)O(2))], show monomeric structures with a distorted square-pyramidal coordination. The two phenyl groups on the five-membered N,N'-chelate ring are both on the same side as the oxo ligand for the exo isomer and on opposite sides for the endo isomer.

exo-[N,N'-Bis(3-tert-butylsalicylidene)-1,2-diphenyl-(RS,SR)-1,2-ethanediyldiaminato]oxovanadium(IV).

The title mononuclear oxovanadium(IV) complex, [VO(C(36)H(38)N(2)O(2))], has a distorted square-pyramidal coordination. The complex was shown to be the exo isomer.

Tetra-micro-acetato-O:O'-bis[(7-azaindole-N)copper(II)].

The title complex, [Cu(2)(C(2)H(3)O(2))(4)(C(7)H(6)N(2))(2)], shows a binuclear cage structure having an inversion centre. There are intramolecular N-H.O hydrogen bonds between the 7-azaindole ligands and the bridging acetate O atoms.

[N,N'-Bis(3-carboxysalicylidene)-1,2-diphenyl-(RR,SS)-1,2-ethanediyldiaminato-O,N,N',O'](methanol-O)oxovanadium(IV) and [N,N'-bis(3-carboxysalicylidene)-2,3-dimethyl-2,3-butanediyldiaminato-O,N,N',O']oxovanadium(IV) monohydrate.

The two title mononuclear oxovanadium (IV) complexes, [VO(C(30)H(22)N(2)O(6))(CH(3)OH)] and [VO(C(22)H(22)N(2)O(6))].H(2)O, respectively, have distorted square-pyramidal coordination and the 3-carboxy groups form intramolecular hydrogen bonds with the coordinated salicyl O atoms. In (I), methanol coordinates to the vanadium atom trans with respect to the oxo ligand.

[N,N'-Bis(salicylidene)-1,2-diphenyl-(RS,SR)-1,2-ethanediaminato]nickel(II).

In crystals of the title compound, [Ni(C(28)H(22)N(2)O(2))], the coordination geometry around the Ni atom is square planar with a slight tetrahedral distortion. The five-membered N,N'-chelate ring adopts a distorted gauche conformation with the two phenyl groups in axial and equatorial orientations.

trans-Diaquabis(N-acetylanthranilato-O,O')copper(II).

The title monomeric copper(II) complex, [Cu(C(9)H(8)NO(3))(2)(H(2)O)(2)], (I), shows a square-planar coordination and has an inversion centre at the Cu atom. The carboxylate group of the N-acetylanthranilate ion acts as a monodentate donor ligand to copper and as an acceptor of an intramolecular O-H.O hydrogen bond from the coordinated water molecule, with an O.O distance of 2.581 (2) A.

catena-Poly[[tetrakis(micro-2,2-dimethylpropionato-O:O')dicopper(II)]-micro-dioxane-O:O'] and catena-poly[[tetrakis(micro-3,3-dimethylbutyrato-O:O')dicopper(II)]-micro-dioxane-O,O'].

The title two compounds, [Cu(2)(C(5)H(9)O(2))(4)(C(4)H(8)O(2))](n), (I), and [Cu(2)(C(6)H(11)O(2))(4)(C(4)H(8)O(2))](n), (II), are isomorphous. The binuclear Cu(II) units have a cage structure and are linked by the dioxane molecules to form a zigzag chain along the c axis. The binuclear copper unit and the dioxane ligand each have a centre of symmetry.

catena-Poly

The two title compounds, [Cu(3)(C(6)H(11)O(2))(6)(C(7)H(9)N)(2)](n), (I), and [Cu(2)(C(5)H(9)O(2))(4)(C(7)H(9)N)(2)], (II), have chain and finite-molecular structures, respectively. In (I), binuclear cage units and mononuclear 2,6-dimethylpyridine complexes, both of which have inversion centres, are arranged alternately and are linked by the carboxylate ions to form one-dimensional chains along the a axis. In (II), the binuclear cage unit has an inversion centre and the coordination geometry around the Cu atom is typical square pyramidal, with 2,6-dimethylpyridine at the apical position.

[Transcervical and transoral approach to clival and upper cervical chordoma: a case report].

The patient, a 48-year-old man, was first admitted in 1981 for the chief complaints of retropharyngeal tumor and anosmia. Computerized tomography scan disclosed destruction of the lower half of the clivus and retropharyngeal tumor predominantly located in the third prevertebral region. The tumor was removed partially via the transcervical approach and was histologically a typical chordoma. Two years later the tumor recurred and was operated on by the same approach. However, only partial removal of the tumor was realized due to difficulties in dissecting the fibrous adhesion. In 1986 (7 years after onset of the symptoms), the patient was readmitted due to severe dysphagia. The sagittal MRI scan demonstrated a huge oval retropharyngeal tumor with precise delineation between the tumor and clivus, clivus upper cervical spine and brain stem. The tumor was extirpated subtotally on the midline via the transoral approach. Dysphagia completely improved postoperatively and the patient regained normal smell sensation. The advantages and disadvantages of the transcervical and transoral approach to clival lesion are discussed and the advantage of the MRI imaging is stressed for preoperative information for the transoral approach.