Participation of the peroxisomal beta-oxidation system in the chain-shortening of PCA16, a metabolite of the cytosine arabinoside prodrug, YNKO1, in rat liver

When PCA16, a metabolite of the cytosine arabinoside prodrug YNKO1, was incubated with isolated rat hepatocytes, time-dependent H2O2 generation was found. When the hepatocytes obtained from clofibrate-treated rat liver were used as an enzyme source, PCA16-dependent production of H2O2 was increased by around 6-fold. The activity of peroxisomal beta-oxidation for PCA16 assayed by H2O2 generation was 3-fold higher than that for palmitic acid, whereas the activity of mitochondrial beta-oxidation for PCA16 assayed by ketone body production was much less than that for palmitic acid. A subcellular distribution study revealed that the distribution of the activities of beta-oxidation and fatty acyl-CoA oxidase for PCA16-CoA coincided with those of cyanide-insensitive palmitoyl-CoA-dependent beta-oxidation and catalase, a marker enzyme of peroxisomes. The profile of the cofactor requirement for beta-oxidation of PCA16-CoA in isolated peroxisomes was similar to that for palmitoyl-CoA oxidation, and the reaction was not inhibited by KCN. The formation of CoA derivative prior to beta-oxidation reaction was essential. HPLC analysis of metabolites after incubation of PCA16-CoA with isolated peroxisomes demonstrated the production of four metabolites, two of which were identified as PCA14 and PCA12 by fast atomic bombardment-mass spectrometry. These results indicate that peroxisomal beta-oxidation participates in the shortening of the alkyl-side chain of PCA16 and plays an important role in the formation of antileukemic cytosine arabinoside from YNKO1.     

A case report of mitral valve regurgitation due to the infective endocarditis associated with the straight back syndrome

A 54 year-old man was admitted to our hospital with a compliant of high fever following the dental treatment. He had the straight thoracic spine with absence of physiological kyphosis. Blood culture was positive for Streptococcus sanguis I. Echocardiography revealed the mitral valve regurgitation with some vegetation at the ruptured chordae tendinae of the posterior leaflet. The operation was performed after the sign of the inflammation was disappeared. We performed the mitral valve reconstruction following the Carpentier's technique. The half of the posterior leaflet was excised, and the annuloplasty and valvuloplasty was done with ease.     

Beneficial effect of diltiazem on pulmonary hypertension in a patient with Hughes-Stovin's syndrome]

A 54 year-old female who had a history of hemoptysis was admitted to our hospital because of dyspnea on effort. Pulmonary arterial pressure was elevated and pulmonary arteriography showed multiple pulmonary arterial aneurysms and occlusion of the left upper lobe pulmonary artery. Systolic pulmonary arterial pressure was 110 mmHg when measured by continuous wave Doppler echocardiography. From the clinical and angiographical findings, we diagnosed this patient as having Hughes-Stovin's syndrome (forme fruste). 30 mg of diltiazem per day was initially used, and 80 mg was used thereafter. After 2 months follow up of the medication with diltiazem, systolic pulmonary arterial pressure decreased from 110 mmHg to 61 mmHg and clinical symptoms improved dramatically.     

Polycationic biocides with pendant active groups: molecular weight dependence of antibacterial activity.

Two types of polycations with pendant active groups were synthesized: one is polymethacrylate containing pendant biguanide units, and the other is poly(vinylbenzyl ammonium chloride). The two polycations were found to exhibit higher bactericidal activity against Staphylococcus aureus than the corresponding monomers. Fractionation of the polycations was successfully performed on gel filtration chromatography, and examination of the antibacterial activity against S. aureus of the well-characterized polymer samples with various molecular weights (MW) revealed that the activity was strongly dependent on the MW of the polycations and that there existed an optimal MW range for the cidal action of the polymeric biocides. Experiments on the lysis of protoplasts of Bacillus subtilis in contact with the polycations have shown that target sites of the polycationic biocides are cytoplasmic membranes of bacteria.     

Mercury-selenium interaction in workers exposed to elemental mercury vapor

Mercury (Hg) and selenium (Se) levels were determined for erythrocytes, plasma and urine of 25 male and 29 female workers exposed to elemental mercury (Hgo) vapor. Interrelationship between the Hg levels and the Se levels was examined by the correlational analysis and the stepwise regression analysis. Indicators of Se status (erythrocyte Se levels, plasma Se levels and urinary Se levels) were closely intercorrelated; similarly, indicators of exposure to Hgo vapor (erythrocyte inorganic Hg levels, plasma Hg levels and urinary Hg levels) were significantly intercorrelated. Since plasma Hg level was one of the significant independent variables in determining the erythrocyte Se and plasma Se levels, Hgo vapor exposure was thought likely to influence the Se metabolism in workers. None of the Se status indicators were significant as determinants of the indicators of Hgo vapor exposure.     

Excretion of 1,2,4-benzenetriol in the urine of workers exposed to benzene

Urine samples were collected from 152 workers (64 men, 88 women) who had been exposed to benzene, 53 workers (men only) exposed to a mixture of benzene and toluene, and 213 non-exposed controls (113 men, 100 women). The samples were analysed for 1,2,4-benzentriol (a minor metabolite of benzene) by high performance liquid chromatography. The time weighted average solvent exposure of each worker was monitored by diffusive sampling technique. The urinary concentration of 1,2,4-benzentriol related linearly to the intensity of exposure to benzene both in men and women among workers exposed to benzene, and was suppressed by toluene co-exposure among male workers exposed to a mixture of benzene and toluene. A cross sectional balance study in men at the end of the shift of a workday showed that only 0.47% of benzene absorbed will be excreted into urine as 1,2,4-benzenetriol, in close agreement with previous results in rabbits fed benzene. The concentration of 1,2,4-benzenetriol in urine was more closely related to the concentration of quinol than that of catechol. The fact that phenol and quinol, but not catechol, are precursors of 1,2,4-benzentriol in urine was further confirmed by the intraperitoneal injection of the three phenolic compounds to rats followed by urine analysis for 1,2,4-benzenetriol.     

An antitumor principle from Euphorbia lathyris

The extract of seeds of Euphorbia lathyris L. showed antitumor activity against Sarcoma 180 ascites in mice. Systematic fractionation of the extract led to the characterization of ingenol-3-hexadecanoate as an active principle, together with an inactive diterpene ingenol-20-hexadecanoate.     

Simultaneous corrections Bentall procedure, mitral valve replacement and sternoplasty for a patient with Marfan's syndrome

A successful case of simultaneous modified Bentall' procedure, MVR and sternoplasty was presented for a 42 years old man of Marfan's syndrome who had funnel chest, combined with mitral regurgitation, aortic regurgitation and annuloaortic ectasia. A few reports of one stage operation for the combination of funnel chest and heart disease in Marfan's syndrome has been published. A median sternotomy was made, with total cardiopulmonary bypass, heart was arrest and cor cooling hypothermia with crystalloid cardioplegic solution. Mitral valve was replaced with #31 B-S prosthetic valve. The ascending aorta proximal to the innominate artery and the aortic valve were replaced en-bloc with composite graft made of a vascular graft and aortic valve prostheses. Coronary artery orifices cut to the button-shaped, were sutured to the composite graft. Finally, sternoplasty was completed through modified Ravitch sterno-elevation. This is the first report in Japanese journals.