Comparative pharmacokinetics of 67Ga among the different routes of injection

The pharmacokinetic study of 67Ga-citrate (67Ga) following intravenous (i.v.), subcutaneous (s.c.) and intraperitoneal (i.p.) injection was performed in anesthetized rats using the repeated blood sampling method by cannulation technique into the external jugular vein. The disappearance of 67Ga from the blood following i.v. and s.c. injection was best fit a three-exponential equation. There was no significant difference between the areas under the curves following i.v. and s.c. injection of 67Ga. In the case of i.p. injection, the disappearance of 67Ga from the blood was described by a two-exponential equation. However, the maximum blood radioactivity was very low, and the disappearance rate of 67Ga from the blood was extremely slow compared to the other routes of injection. The conclusion from these results was that s.c. injection was as suitable as i.v. injection, but i.p. injection was not appropriate for the distribution study of 67Ga such as scintigraphy or autoradiography. However, i.p. route may be available for a special experiment which needs the long-time retention of 67Ga in the blood.     

Selective flow-injection determination of methanol in the presence of ethanol based on a multi-enzyme system with chemiluminescence detection

A highly selective flow-injection system was developed for the determination of methanol. The system consisted of three immobilized enzymes with luminol chemiluminescence detection. First, methanol was oxidized in the presence of alcohol oxidase to yield formaldehyde and hydrogen peroxide. The hydrogen peroxide produced was then destroyed by catalase. The formaldehyde formed in the first stage was further oxidized by NAD⁺-formaldehyde dehydrogenase. The NADH formed was oxidized by 1-methoxy-5-methylphenazinium methylsulphate (1-MPMS), and finally the reduced 1-MPMS was spontaneously oxidized and hydrogen peroxide was produced. The concentration of the hydrogen peroxide produced, which was proportional to the initial concentration of methanol, was determined by luminol chemiluminescence. The determination range was from 0.1 to 100 mg l⁻¹ and the response time was less than 2 min per sample with a relative standard deviation of less than 3%. The system showed good selectivity for methanol; the response was ca. 50 times higher than for ethanol.     

1,3,8,10-Tetrahydro-2,9-diazadibenzo[cd,lm]perylenes: synthesis of reduced perylene bisimide analogues

A unique family of 1,3,8,10-tetrahydro-2,9-diazadibenzo[cd,lm]perylenes (THDAP) was prepared through a new synthetic strategy. Completion of the synthesis was achieved in several steps from commercially available perylene-3,4,9,10-tetracarboxylic dianhydride via reactions between 3,4,9,10-tetra(chloromethyl)perylene and primary amines. The successful use of a variety of primary amines in the reactions indicated that the synthetic approach provides a rich opportunity to produce new functionalized perylene derivatives.     

General and practical catalytic enantioselective Strecker reaction of ketoimines: significant improvement through catalyst tuning by protic additives

Significant improvement in enantioselectivity and catalyst activity was achieved for the catalytic enantioselective Strecker reaction. Using a catalyst (1-2.5 mol %) prepared from Gd(OⁱPr)₃ and d-glucose derived ligand 1, and in the presence of 2,6-dimethylphenol as an additive, high enantioselectivity was obtained from a wide range of ketoimines, including heteroaromatic and cyclic ketoimines. The new method was applied to an efficient catalytic asymmetric synthesis of sorbinil, a therapeutic agent for diabetic complications.     

Organotrichlorogermane synthesis by the reaction of elemental germanium, tetrachlorogermane and organic chloride via dichlorogermylene intermediate

Organotrichlorogermanes were synthesized by the reaction of elemental germanium, tetrachlorogermane and organic chlorides, methyl, propyl, isopropyl and allyl chlorides. Dichlorogermylene formed by the reaction of elemental germanium with tetrachlorogermane was the reaction intermediate, which was inserted into the carbon-chlorine bond of the organic chloride to give organotrichlorogermane. When isopropyl or allyl chloride was used as an organic chloride, organotrichlorogermane was formed also in the absence of tetrachlorogermane. These chlorides were converted to hydrogen chloride, which subsequently reacted with elemental germanium to give the dichlorogermylene intermediate. The reaction of elemental germanium, tetrachlorogermane and organic chlorides provides a simple and easy method for synthesizing organotrichlorogermanes, and all the raw materials are easily available.     

Substoichiometric isotope-dilution determination of sulphur after conversion to methylene blue and ion-pair extraction with dodecyl sulphate

The proposed substoichiometric determination of sulphur includes two key steps: conversion of sulphur to methylene blue and ion-pair extraction of methylene blue into chloroform with a substoichiometric amount of dodecyl sulphate. The method, combined with isotope dilution is applied to the determination of total sulphur in NBS SRM Citrus Leaves and in a seaweed sample (Laminaria religiosa Miyabe). The mean values obtained were 0.401±0.008% S (RSD 2%; n=9; certified value 0.407±0.009%) for the SRM, and 0.756±0.012% S (RSD 1.6%; n=5) for the seaweed. A sample of 0.5–1 g containing ca. 100 μg of sulphur can be analysed.     

Abnormal protein spots revealed by two-dimensional electrophoresis in mycoplasma-infected human fibroblasts

Six new protein spots were detected by two-dimensional electrophoresis in cultured human fibroblasts infected with mycoplasma. No changes were observed in other protein spots present in normal and pathological cells. After treatment with an antimycoplasma drug for a week, the new spots disappeared and the cells became negative for mycoplasma stain.     

Mechanistic studies on the binding of nitric oxide to a synthetic heme-thiolate complex relevant to cytochrome p450

The synthetic heme-thiolate complex (SR) in methanol binds nitric oxide (k(on) = (2.7 +/- 0.2) x10(6) M(-)(1) s(-)(1) at 25 degrees C) to form SR(NO). The binding of NO to the SR complex in a noncoordinating solvent, such as toluene, was found to be almost 3 orders of magnitude faster than that in methanol. The activation parameters DeltaH(), DeltaS(), and DeltaV() for the formation of SR(NO) in methanol are consistent with the operation of a limiting dissociative mechanism, dominated by dissociation of methanol in SR(MeOH). In the presence of an excess of NO, the formation of SR(NO) is followed by subsequent slower reactions. The substantially negative activation entropy and activation volume values found for the second observed reaction step support an associative mechanism which involves attack of a second NO molecule on the thiolate ligand in the initially formed SR(NO) complex. The following slower reactions are strongly accelerated by a large excess of NO or by the presence of NO(2)(-) in the SR/NO reaction mixture. They can be accounted for in terms of dynamic equilibria between higher nitrogen oxides (NO(x)()) and reactive SR species, which lead to the formation of a nitrosyl-nitrite complex of SR(Fe(II)) as the final product. This finding is clearly supported by laser flash photolysis studies on the SR/NO reaction mixture, which do not reveal simple NO photolabilization from SR(Fe(III))(NO), but rather involve the generation of at least three photoinduced intermediates decaying with different rate constants to the starting material. The species formed along the proposed reaction pathways were characterized by FTIR and EPR spectroscopy. The results are discussed in terms of their relevance for the biological function of cytochrome P450 enzymes and in context of results for the reaction of NO with imidazole- and thiolate-ligated iron(III) hemoproteins.     

Pressure dependence of NMR spectroscopy for studying intermolecular interactions 1H NMR in organic solvents involving the nitroxide radical

Pressure effects on ¹H chemical shifts and relaxation rates in organic solvents containing the nitroxide radical have been observed. ¹H chemical shifts with pressure and pressure-broadenings for hydrogen bonding between proton-donor molecules and the nitroxide radical have been observed.     

Interaction of pentoxifylline with human erythrocytes. III. Comparison of fluidity change of erythrocyte membrane caused by S-adenosyl-L-methionine with that by pentoxifylline

The change in fluidity by adding pentoxifylline to erythrocyte membranes was compared with that caused by S-adenosyl-L-methionine (SAM) by the method of electron spin resonance (ESR) spectroscopy. When SAM or pentoxifylline was added externally to the erythrocyte suspension (outside), the fluidity of the membrane bilayer was increased after incubation at 37 degrees C. However, the fluidity change in the inner part of the bilayer was relatively small compared to that in its outer part. These fluidity changes were dependent on the incubation time and the temperature. When the erythrocyte suspension was preincubated overnight at 4 degrees C in the presence of drugs (inside), the fluidity of the inner part of the membrane changed significantly. Nevertheless, that of the outer part of the lipid bilayer was not affected. Such an asymmetric fluidity change in the lipid bilayer was not observed by the addition of other xanthine derivatives such as caffeine, theophylline and theobromine. S-Adenosyl-L-homocysteine suppressed and MgCl2 enhanced the increase of the membrane fluidity by SAM or pentoxifylline. Furthermore, the effects of SAM and pentoxifylline on erythrocyte deformability were determined by a filtering technique method. In increasing order the additive effects of SAM and pentoxifylline on the erythrocyte filterability were SAM (outside) less than pentoxifylline (inside) less than pentoxifylline (outside) less than SAM (inside). These results suggest that pentoxifylline also affects the membrane fluidity through the enzymatic methylation of phospholipids.