Effects of Mean Normal Stress and Microstructural Properties on Deformation Properties of Ultrahigh-Strength TRIP-Aided Steels with Bainitic Ferrite and/or Martensite Matrix Structure.

The effects of mean normal stress on the deformation properties such as the strain-hardening, strain-induced martensite transformation, and micro-void initiation behaviors of low-carbon ultrahigh-strength TRIP-aided bainitic ferrite (TBF), bainitic ferrite/martensite (TBM), and martensite (TM) steels were investigated to evaluate the various cold formabilities. In addition, the deformation properties were related to the microstructural properties such as the matrix structure, retained austenite characteristics, and second-phase properties. Positive mean normal stress considerably promoted strain-induced martensite transformation and micro-void initiation, with an increased strain-hardening rate in an early strain range in all steels.

Effects of atorvastatin and pravastatin on glucose tolerance, adipokine levels and inflammatory markers in hypercholesterolaemic patients.

Several randomized clinical trials have suggested that atorvastatin and pravastatin may differ in terms of their pleiotropic effects. To verify this, we compared the effects of both statins on glucose tolerance, adipokine concentrations and inflammatory markers. A total of 36 hypercholesterolaemic patients without known coronary heart disease (CHD) were enrolled in an open-label, randomized, crossover study.

Clearance of imidapril, an Angiotensin-converting enzyme inhibitor, during hemodialysis in hypertensive renal failure patients: comparison with quinapril and enalapril.

The dialyzability of imidaprilat, an active metabolite of the angiotensin-converting enzyme (ACE) inhibitor imidapril, was determined and compared with those of enalaprilat and quinaprilat in hypertensive patients on chronic hemodialysis. Imidapril (5 mg/d, n = 6), enalapril (2.5 mg/d, n = 6), or quinapril (2.

Interaction between grapefruit juice and hypnotic drugs: comparison of triazolam and quazepam.

Objective: Grapefruit juice (GFJ) inhibits cytochrome P450 (CYP) 3A4 in the gut wall and increases blood concentrations of CYP3A4 substrates by the enhancement of oral bioavailability. The effects of GFJ on two benzodiazepine hypnotics, triazolam (metabolized by CYP3A4) and quazepam (metabolized by CYP3A4 and CYP2C9), were determined in this study.

Methods: The study consisted of four separate trials in which nine healthy subjects were administered 0.

Recurrence of hepatic artery thrombosis following acute tacrolimus overdose in pediatric liver transplant recipient.

Acute overdose of tacrolimus appears to cause no or minimal adverse clinical consequences. We encountered a pediatric case who underwent liver transplantation associated with hepatic artery thrombosis (HAT), which recurred following acute tacrolimus overdose. A 10-month-old girl underwent living-related liver transplantation because of biliary atresia.

Effects of grapefruit juice on the pharmacokinetics of pitavastatin and atorvastatin.

Aims: To compare the effects of grapefruit juice (GFJ) on the pharmacokinetics of pitavastatin and atorvastatin.

Methods: In a randomized, four-phase crossover study, eight healthy subjects consumed either GFJ or water t.i.

Exaggerated liver injury induced by ischemia-reperfusion in spontaneously hypertensive rats.

Background: The functions of polymorphonuclear leukocytes (PMNs), which play a critical role in organ damage, are primed in patients with essential hypertension and spontaneously hypertensive rats (SHR). Hepatic ischemia-reperfusion (I/R) injury is shown to be caused and aggravated by the PMNs. We examined whether the hepatic I/R injury was exaggerated in SHR.

Dosing time-dependent effect of temocapril on the mortality of stroke-prone spontaneously hypertensive rats.

This study was undertaken to evaluate a dosing time-dependent effect of temocapril, an angiotensin-converting enzyme (ACE) inhibitor, on the mortality of stroke-prone spontaneously hypertensive rats (SHRSP). Temocapril (1 mg/kg/day) prolonged the survival rate of these animals, with a maximum effect after dosing at the early resting period and a minimum effect after dosing at the early active period. The pharmacokinetics of temocaprilat, an active metabolite of temocapril, did not differ significantly between the two dosing times.

Daily rhythms of P-glycoprotein expression in mice.

Recent studies have shown the gene expression of several transporters to be circadian rhythmic. However, it remains to be elucidated whether the expression of P-glycoprotein, which is involved in the transport of many medications, undergoes 24 h rhythmicity. To address this issue, we investigated daily profiles of P-glycoprotein mRNA and protein levels in peripheral mouse tissues.

Different effects of imidapril and enalapril on aminopeptidase P activity in the mouse trachea.

It has been reported that the incidence of angiotensin-converting enzyme (ACE) inhibitor-related dry cough is significantly less with the ACE inhibitor imidapril than with the ACE inhibitor enalapril in hypertensive patients. Bradykinin (BK) in the trachea is believed to play some role in this adverse effect. The present study was undertaken to evaluate the effects of imidapril and enalapril on the activity of aminopeptidase P (APP), one of the BK-metabolizing enzymes, in the mouse trachea.

Chronopharmacology of morphine in mice.

Dosing-time-dependent changes in the effect and toxicity of morphine were examined in mice housed under alternating 12 h light (07:00 to 19:00 h) and dark (19:00 to 07:00 h) cycles. Morphine (0.5 mg/kg) was injected intraperitoneally (i.

Elevated blood concentrations of calcineurin inhibitors during diarrheal episode in pediatric liver transplant recipients: involvement of the suppression of intestinal cytochrome P450 3A and P-glycoprotein.

We encountered two cases of pediatric living-related liver transplant recipients who showed increases in blood concentration of cyclosporine or tacrolimus, a dual substrate for cytochrome P450 (CYP) 3A and P-glycoprotein (P-gp), during a diarrheal episode. To investigate the effect of intestinal inflammation on the metabolic and efflux pump activities, we conducted the experiments using the lipopolysaccharide (LPS)-induced intestinal damage model. Intestinal epithelial CYP3A activity was assessed by nifedipine oxidation using intestinal epithelial microsomes in rat.

Renal protective effect of YM598, a selective endothelin type A receptor antagonist.

We have investigated the protective effect of YM598, a selective endothelin type A receptor antagonist, against an endothelin-1-induced proliferation of rat mesangial cells and renal function in Otsuka Long-Evans Tokushima Fatty (OLETF) rats, an animal model of type II diabetes. YM598, but not K-8794, a selective endothelin type B receptor antagonist, inhibited the endothelin-1-induced proliferation of cultured mesangial cells derived from intact Wistar rats in a concentration-dependent manner. YM598 (0.

Case report of unchanged tacrolimus clearance in a hypoxemic pediatric liver transplant recipient with hepatopulmonary syndrome.

Reductions in hepatic oxygen supply may reduce the oxidative metabolism of drugs, including tacrolimus. We encountered a patient (2.3-year-old girl) with hypoxemia [arterial oxygen tension (PaO2) 40.

Chronotoxicity of nedaplatin in rats.

Chronotoxicologic profiles of nedaplatin, a platinum compound, were evaluated in rats maintained under a 12 light/12 dark cycle with light from 07:00h to 19:00 h. Nedaplatin (5 mg/kg) was injected intravenously, once a week for 5 weeks at 08:00h or 20:00h. The suppression of body weight gain and reduction of creatinine clearance were significantly greater with the 20:00h than 08:00h treatment.

Effect of probucol on the oral bioavailability of cyclosporine A.

We have previously reported the reduction in oral bioavailability of cyclosporine A (CsA) by probucol, a lipid-lowering drug. To evaluate the mechanism, we examined the effect of probucol on the transport of CsA across Caco-2 cell monolayers, on the influence of CsA pharmacokinetics in rats, and on the change of ultraviolet-absorption spectrum of the drug. Pretreatment with probucol (50 microM) inhibited (P < 0.

Sustained plasma fibrinogen elevation in subtotal nephrectomized rats: effect of cilazapril, an angiotensin-converting enzyme inhibitor.

The present study was undertaken to examine whether plasma fibrinogen persistently elevates in subtotal nephrectomized rats, an animal model with inflammatory renal changes. Eight weeks after the induction of 5/6 nephrectomy in male Wistar rats, plasma fibrinogen concentration was determined for the next 12 weeks in the animals received vehicle or an angiotensin-converting enzyme inhibitor, cilazapril (1 or 10 mg/kg per day) orally. In the vehicle-treated nephrectomized rats, plasma fibrinogen concentration significantly (P<0.

Evaluation of chronopharmacodynamics of indomethacin by the kaolin-induced pain model in mice.

We previously showed that the kaolin-induced writhe reaction exhibits 24 h variation with a peak at the end of the resting period (14:00-18:00 h) in mice maintained under light from 07:00 to 19:00 h. In this study, we used this model to evaluate the administration-time-dependent (chronopharmacodynamic) effect of indomethacin. Indomethacin (0.

Dosing-time-dependent variation in biliary excretion of flomoxef in rats.

We previously reported that the biliary excretion of flomoxef, an oxacephem antibiotic, was greater after dosing at 21:00 than at 09:00 h in diurnally active human subjects. The present study was undertaken to examine whether the biliary excretion of flomoxef is also dependent on its dosing time in rats. Adult male Wistar rats were housed under light on at 07:00 h and off at 19:00 h.

Hepatic venous stenosis-related reduction of cyclosporin clearance in a pediatric patient after liver transplantation.

A 20-month-old girl with Alagille syndrome developed stenosis of hepatic venous anastomosis after living related-donor liver transplantation. Cyclosporin (a microemulsion formulation) was given orally at a dose of 50 mg twice daily, and the trough blood concentration was relatively stable. Before balloon angioplasty of the hepatic vein, trough cyclosporin blood concentrations became elevated and consequently, the dosage was reduced to 15 mg twice daily.

Severe low back pain due to retroperitoneal abscess formation in diabetic patients.

We report two cases of diabetic patients with severe low back pain associated with retroperitoneal abscesses. In the first case, multiple retroperitoneal and spinal epidural abscesses were detected. Paraplegia due to the spinal epidural abscess was not relieved by drainage of the abscess and subsequent antibiotic therapy.

Renal protective effect of YM598, a selective endothelin ET(A) receptor antagonist, against diabetic nephropathy in OLETF rats.

We have investigated the effect of potassium (E)-N-[6-methoxy-5-(2-methoxyphenoxy)-2-(pyrimidin-2-yl) pyrimidin-4-yl]-2-phenylenthenesulfonamidate (YM598), a selective endothelin ET(A) receptor antagonist, on renal function in Otsuka Long-Evans Tokushima Fatty (OLETF) rats, an animal model of type II diabetes. YM598 (0.1 or 1 mg kg(-1)), enalapril (5 mg kg(-1)), an angiotensin-converting enzyme inhibitor, or vehicle was administered once daily by gastric gavage to 22-week-old male Otsuka Long-Evans Tokushima Fatty rats for 32 weeks.

Angiotensin II attenuates the vasodilating effect of a nitric oxide donor, glyceryl trinitrate: roles of superoxide and angiotensin II type 1 receptors.

Objective: The development of tolerance to organic nitrates limits their usefulness in the treatment of heart disease. Activation of the renin-angiotensin system by heart failure itself and by nitrate therapy may be one possible mechanism underlying nitrate tolerance. We investigated the effect of subpressor doses of angiotensin II on the vasodilating effect of glyceryl trinitrate in human forearm resistance vessels of healthy male subjects by using venous occlusion strain-gauge plethysmography.

P-glycoprotein-mediated drug secretion in mouse proximal tubule perfused in vitro.

To examine the functional significance of drug-transporting P-glycoprotein (P-gp), studies were conducted in the isolated and perfused proximal tubule S2 segment from mice disrupting both mdr1a and mdr1b genes [mdr1a/1b(-)(-)] and their wild-type mice. Efflux of the intracellular fluorescence of rhodamine 123, a fluorescence substrate of P-gp, into the lumen was measured, and the decay half-time of the intracellular fluorescence (T(1/2)) as an index of the drug-transporting P-gp activity was regarded. In the wild-type mice, the T(1/2) was 34 +/- 4 s (n = 36) at the basal period and was increased to 434 +/- 41 s by the addition of luminal verapamil, a P-gp inhibitor.