Degradation of lignin and lignin model compound under sulfate reducing condition.

The release of depolymerization products of lignin during the degradation of lignocellulsic material under sulfate reducing condition was investigated. In addition, we investigated the fate of the most common (beta-O-4) link present in lignin under sulfate reducing condition, using a lignin model compound. The method of investigation was based on the selective inhibition of microbial uptake of released aromatic phenolic compounds, depolymerization product of lignin, by toluene.

Impact of pre-stent plaque debulking for chronic coronary total occlusions on restenosis reduction.

Background: While stenting improves the long-term angiographic outcomes of successfully recanalized chronic coronary total occlusions (CTO), the restenosis rate still remains high. The massive plaque burden in CTO is considered to be one of the causes of in-stent restenosis.

Methods: We examined the pre-stent plaque debulking strategy with high-speed rotational atherectomy (RA) for 50 CTO (Thrombolysis in Myocardial Infarction flow grade 0; estimated occlusive duration, 3 months).

Hydrolysis of newspaper polysaccharides under sulfate reducing and methane producing conditions.

The initial decomposition rates of cellulose and hemicellulose were measured using toluene to specifically inhibit the microbial uptake of hydrolysis products during the degradation of newspaper under sulfate reducing and methane producing conditions. The amount of glucose and xylose accumulation in the first 2 weeks of incubation period was higher in the sulfate reducing condition compared to the methane producing condition. It was estimated that 28 and 6% of initially loaded cellulose in the sulfate reducing condition and the methane producing condition was hydrolyzed, respectively.

Cellular characterization of an in-vitro cell culture model of seal-induced cardiac ischaemia.

The lack of a well-characterized in-vitro cell culture model of load-induced cardiac ischaemia has hampered investigations into the mechanism of ischemic injury. We therefore developed a new in-vitro model of cardiac ischaemia that mimics distinct features of ischaemic injury. Neonatal rat heart cells were cultured in a sealed flask for 24-72 h.

Role of osmoregulation in the actions of taurine.

Taurine regulates an unusual number of biological phenomena, including heart rhythm, contractile function, blood pressure, platelet aggregation, neuronal excitability, body temperature, learning, motor behavior, food consumption, eye sight, sperm motility, cell proliferation and viability, energy metabolism and bile acid synthesis. Many of these actions are associated with alterations in either ion transport or protein phosphorylation. Although the effects on ion transport have been attributed to changes in membrane structure, they could be equally affected by a change in the activity of the affected transporters.

Specific determination of urinary 6beta-hydroxycortisol and cortisol by liquid chromatography-atmospheric pressure chemical ionization mass spectrometry.

The urinary 6beta-hydroxycortisol to cortisol ratio is believed to be a noninvasive index of cytochrome P450 3A activity. For precise assessment of the ratio in human urine, we have developed a reversed-phase high-performance liquid chromatography-atmospheric pressure chemical ionization mass spectrometry method. The selective method was accurate and reproducible with intra- and inter-day precision of variation coefficients of less than 8%.

Taurine attenuates hypertrophy induced by angiotensin II in cultured neonatal rat cardiac myocytes.

The effect of taurine on angiotensin II-induced changes in cell morphology and biochemistry of the cultured neonatal cardiomyocyte was examined. Angiotensin II (1-100 nM) alone caused a slow increase in the surface area of the myocyte accompanied by an induction of the expression of atrial natriuretic peptide (ANP) and an upregulation of transforming growth factor beta(1) gene (TGF-beta(1)). The signaling pathway of angiotensin II (1-100 nM) was found to proceed through protein kinase C and the rapid activation of mitogen-activated protein (MAP) kinases.

Interaction between the actions of taurine and angiotensin II.

The amino acid, taurine, is an important nutrient found in very high concentration in excitable tissue. Cellular depletion of taurine has been linked to developmental defects, retinal damage, immunodeficiency, impaired cellular growth and the development of a cardiomyopathy. These findings have encouraged the use of taurine in infant formula, nutritional supplements and energy promoting drinks.

Distribution and properties of endo-beta-1,4-glucanase from a lower termite, Coptotermes formosanus (Shiraki).

A multi-enzyme distribution of endo-beta-1,4-glucanase activity was found in the digestive system of a worker caste of the lower termite Coptotermes formosanus (Shiraki) by zymogram analysis. Its distribution analysis demonstrated that about 80% of this activity was localized in salivary glands from where only one component (EG-E) was secreted into the digestive tract. EG-E was isolated by a combination of chromatographic and electrophoretic techniques.

The decreased in vivo clearance of CYP2D6 substrates by CYP2D6*10 might be caused not only by the low-expression but also by low affinity of CYP2D6.

CYP2D6 exhibits genetic polymorphism with interindividual differences in metabolic activity. We have found a significant influence on the pharmacokinetics of venlafaxine by the CYP2D6*10 allele in a Japanese population. CYP2D6.

The impact of the CYP2D6 and CYP2C19 genotypes on venlafaxine pharmacokinetics in a Japanese population.

Objective: The cytochrome P450 isozymes CYP2D6 and CYP2C19 exhibit genetic polymorphism in human, including a marked interethnic difference. As the functional status of the isozymes CYP2D6 and CYP2C19 have an impact on the pharmacokinetics of some antidepressants, we investigated whether the disposition of venlafaxine was affected by the CYP2D6 and CYP2C19 genotypes.

Methods: Twenty-eight adult Japanese men in good health participated in this study.

Circadian variation of the urinary 6beta-hydroxycortisol to cortisol ratio that would reflect hepatic CYP3A activity.

Objectives: Chronopharmacokinetics of drugs metabolized by cytochrome P450 3A (CYP3A) has been reported recently; however, little is studied on intra-individual circadian variation in CYP3A activity in human. The aim of this study was to assess the intra-individual diurnal variation and day-to-day variation of the urinary 6beta-hydroxycortisol to cortisol ratio, a noninvasive index of human CYP3A activity.

Methods: Urine samples from ten healthy Japanese men were collected over four time intervals (0900 hours to 1300 hours, 1300 hours to 1700 hours, 1700 hours to 2100 hours and 2100 hours to 0900 hours) on days 1, 5 and 14 to verify diurnal variation, and 24-h urine was collected to study day-to-day variation over 2 weeks.

Slow N-acetyltransferase 2 genotype affects the incidence of isoniazid and rifampicin-induced hepatotoxicity.

Setting: Japanese in-patients with pulmonary tuberculosis and normal liver function receiving treatment with isoniazid and rifampicin (INH + RMP).

Objective: To elucidate the relationship between N-acetyltransferase 2 (NAT2) genotype and the incidence of isoniazid + rifampicin-induced hepatotoxicity.

Design: Prospective study.

Quantitative analysis of constitutive and inducible CYPs mRNA expression in the HepG2 cell line using reverse transcription-competitive PCR.

Drug interactions which affect drug metabolism are of clinical importance. It is, however, difficult to estimate drug interactions in human from results obtained in animal experiments. In our previous study, we demonstrated that a combination of the HepG2 cell line and semiquantitative reverse transcription-PCR (RT-PCR) could be used to evaluate the degree of CYP3A mRNA induction by various drugs.

Metallothionein acts as a cytoprotectant against doxorubicin toxicity.

The protective role of metallothionein (MT) against the myocardiotoxicity and hepatotoxicity of doxorubicin (Dox) was investigated in mice. Dox-induced elevations of plasma creatine kinase activity, a measure of myocardiac damage, and plasma glutamate pyruvate transaminase activity, reflecting hepatic damage, were prevented by pretreatment with an MT inducer. Pretreatment with zinc induced MT in the liver and heart, thereby reducing Dox toxicity in these two organs.

Relationship between mRNA levels quantified by reverse transcription-competitive PCR and metabolic activity of CYP3A4 and CYP2E1 in human liver.

Reverse transcription-competitive polymerase chain reaction is a powerful and sensitive tool for quantifying the absolute amount of mRNA. Using this method with beta-actin as the standard, we measured the mRNA level of CYP3A and CYP2E1 isoforms in human livers. We also determined the metabolic activities for both CYP isoforms.

Effects of antisense oligonucleotides to the cardiac Na+/Ca2+ exchanger on calcium dynamics in cultured cardiac myocytes.

The present study was designed to explore the role of the Na+/Ca2+ exchanger on spontaneous beating of cultured cardiac myocytes. Antisense oligonucleotides (AS) based on the sequence of the cardiac Na+/Ca2+ exchanger were used to decrease expression of this Ca2+ transporting protein in cardiac myocytes. An application of AS (10 microM) caused an increase in beating rate of myocytes within 6-24 h.

Effect of the CYP2D6*10 genotype on venlafaxine pharmacokinetics in healthy adult volunteers.

Aims: Interindividual differences in the pharmacokinetics of venlafaxine, a new antidepressant, were shown during early clinical trials in Japan. Venlafaxine is metabolized mainly by CYP2D6 to an active metabolite, O-desmethylvenlafaxine (ODV). Therefore, the influence of the CYP2D6 genotypes on venlafaxine pharmacokinetics was examined in a Japanese population.

CYP2C19 genotypes and omeprazole metabolism after single and repeated dosing when combined with clarithromycin.

Objectives: Omeprazole is metabolized mainly by CYP2C19 which has two major mutations (CYP2C19*2 in exon5 and CYP2C19*3 in exon4) associated with the poor metabolizer (PM) phenotype. The aim of this study was to examine the relationship between genetic polymorphism of CYP2C19 and metabolism of omeprazole administrated as a single dose or as repeated-doses, which were in both cases co-administered with clarithromycin.

Methods: Twelve healthy Japanese subjects were typed for CYP2C19 polymorphism.

Evaluation of induction of CYP3A mRNA using the HepG2 cell line and reverse transcription-PCR.

Cytochrome P-450 3A (CYP3A) is a drug-metabolizing enzyme dominant in the human liver. We have designed a useful method for evaluation of induction of CYP3A mRNA by various drugs using HepG2 cells known to retain liver-cellular functions. Using semi-quantitative reverse transcription-PCR (RT-PCR), we demonstrated that cultured HepG2 cells constitutively expressed CYP3A mRNA.

Interaction of citrus juices with pranidipine, a new 1,4-dihydropyridine calcium antagonist, in healthy subjects.

Objectives: The study was conducted to investigate whether oral co-administration with citrus juices significantly affects the pharmacokinetics and/or pharmacodynamics of pranidipine, a new 1,4-dihydropyridine calcium antagonist, in healthy male subjects. Grapefruit juice and orange juice, which were both commercially available, were used in this study.

Methods: Sixteen healthy male Japanese subjects participated in this study and were divided into two groups for grapefruit juice and orange juice treatment.

Shape and size changes induced by taurine depletion in neonatal cardiomyocytes.

Taurine is a very important organic osmolyte in most adult cells. Because of this property it has been proposed that large changes in the intracellular content of taurine can osmotically stress the cell, causing changes in its size and shape. This hypothesis was examined by measuring cell dimensions of taurine deficient cardiomyocytes using confocal microscopy.

Renal excretory responses of taurine-depleted rats to hypotonic and hypertonic saline infusion.

Male Wistar-Kyoto rats were given either tap water (control) or 3% beta-alanine (taurine-depleted) for three weeks. To prepare for the kidney function studies, the animals were then implanted with femoral vessels and bladder catheters. Two days after surgery, each rat was given an intravenous infusion of saline at the rate of 50 microliter/min and urine samples were collected at specific time intervals.

Effect of taurine depletion on angiotensin II-mediated modulation of myocardial function.

Taurine depletion was induced by either incubation of isolated myocytes with 5 mM beta-alanine or feeding rats with water containing 3% beta-alanine. Hearts of taurine depleted rats exhibited an impairment in myocardial relaxation, associated with a decrease in Na(+)-Ca2+ exchanger activity. Exposure of the heart to angiotensin II, an activator of the Na(+)-Ca2+ exchanger, eliminated the relaxation defect.