Chronopharmacology of angiotensin II-receptor blockers in stroke-prone spontaneously hypertensive rats.

Protective effect of valsartan (Val), an angiotensin II (AII)-receptor blocker (ARB), against organ damage is reported to depend on the dosing time in hypertensive patients. Dosing-time-dependent effect of Val on survival of stroke-prone spontaneously hypertensive rats (SHRSP) under a 12-h lighting cycle was examined. Val (4 mg/kg per day) and olmesartan medoxomil (OM) (1 mg/kg per day), another ARB with a slower dissociation from the AII receptor, were given once daily at 2, 8, 14, or 20 HALO (hours after lights on).

Chronopharmacology of Angiotensin II-receptor Blockers in Stroke-Prone Spontaneously Hypertensive Rats.

Protective effect of valsartan (Val), an angiotensin II (AII)-receptor blocker (ARB), against organ damage is reported to depend on the dosing time in hypertensive patients. Dosing-time-dependent effect of Val on survival of stroke-prone spontaneously hypertensive rats (SHRSP) under a 12-h lighting cycle was examined. Val (4 mg/kg per day) and olmesartan medoxomil (OM) (1 mg/kg per day), another ARB with a slower dissociation from the AII receptor, were given once daily at 2, 8, 14, or 20 HALO (hours after lights on).

Beta-catenin induces beta-TrCP-mediated PER2 degradation altering circadian clock gene expression in intestinal mucosa of ApcMin/+ mice.

Proliferation of intestinal epithelial cells is rhythmic throughout the day. This temporal organization occurs through the interaction between the endogenous peripheral circadian clock and pathways controlling cell cycle progression. Per2, a core clock gene with tumour suppresser function, is critical to clock function and to the regulation of cellular proliferation.

Successful pediatric living donor liver transplantation from carrier to carrier of hereditary butyrylcholinesterase variant.

Hypocholinesterasemia is often observed clinically, especially in various liver diseases. Not well known, however, is the fact that some patients have a hereditary BChE variant. Little has been reported on liver transplants associated with this hereditary BChE variant.

Developmental abnormalities in multiple proliferative tissues of Apc(Min/+) mice.

Germ-line mutation of the Apc gene has been linked to familial adenomatous polyposis (FAP) that predisposes to colon cancer. Apc(Min/+) mice, heterozygous for the Apc gene mutation, progressively develop small intestinal tumours in a manner that is analogous to that observed in the colon of patients with FAP (Su et al. 1992; Fodde et al.

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.

Dosing-time-dependent differences in lipopolysaccharide-induced liver injury in rats.

Dosing-time-dependent differences in lipopolysaccharide (LPS)-induced liver injury were examined in rats housed under a 12 h light : dark (LD) cycle. LPS (5 mg/kg) was intravenously injected into different groups of rats at 2, 14, or 20 h after light on (HALO). Elevations in serum liver enzymes after 14 HALO were significantly greater than those after 2 HALO.

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.

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.

ACE inhibitors and chronotherapy.

Chronotherapy can improve the effectiveness and reduce the adverse reactions of drugs and actually is used for several conditions including cardiovascular diseases. Although angiotensin converting enzyme (ACE) inhibitors are available for the therapy of patients with hypertension and/or heart failure, these agents have some characteristic adverse effects such as angioedema and dry cough. It has been reported that the dosing of ACE inhibitor at an inactive period has a better protective effect against cardiac hypertrophy in hypertensive rats, and changing dosing time from morning to evening reduces the severity and frequency of the drug-induced dry cough of hypertensive patients treated in the morning.

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.

Drug interaction between St John's Wort and quazepam.

Aim: St John's Wort (SJW) enhances CYP3A4 activity and decreases blood concentrations of CYP3A4 substrates. In this study, the effects of SJW on a benzodiazepine hypnotic, quazepam, which is metabolized by CYP3A4, were examined.

Methods: Thirteen healthy subjects took a single dose of quazepam 15 mg after treatment with SJW (900 mg day(-1)) or placebo for 14 days.

Partial protective effect of Y-27632, a Rho kinase inhibitor, against hepatic ischemia-reperfusion injury in rats.

(+)-(R)-trans-4-(1-aminoethyl)-N-(4-pyridyl)-cyclohexanecarboxamide dihydrochloride (Y-27632), a Rho kinase inhibitor, has a suppressive effect on the functions of polymorphonuclear leukocytes. In this study, the influence of Y-27632 on ischemia-reperfusion injury of the liver was examined in rats. Y-27632 (3 mg/kg) or vehicle alone was intravenously injected into rats 60 min before occlusion.

Pravastatin prevents arrhythmias induced by coronary artery ischemia/reperfusion in anesthetized normocholesterolemic rats.

HMG-CoA reductase inhibitors (statins) have been shown to decrease cardiovascular mortality. Since ventricular tachyarrhythmias are closely related to cardiovascular mortality, we tested effects of the hydrophilic statin pravastatin and the lipophilic statin fluvastatin in a rat arrhythmia model of ischemia/reperfusion and simultaneously measured serum total cholesterol level. Anesthetized rats were subjected to 5-min ischemia and 10-min reperfusion after chronic administration of oral pravastatin (0.

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.

Stereoselective pharmacokinetics of amlodipine in elderly hypertensive patients.

Amlodipine is a dihydropyridine calcium antagonist and is widely used for the treatment of cardiovascular diseases. Amlodipine has two stereoisomers [R(+), S(-)], and only the S(-) isomer exerts vasodilating action. In this preliminary study, amlodipine (5 mg) was given to three elderly hypertensive patients once daily for 10 days.

Vasoconstricting effect of angiotensin II in human hand veins: influence of aging, diabetes mellitus and hypertension.

We examined human hand veins to determine whether venoconstricting response to angiotensin II (Ang II) and noradrenaline (NA) was influenced by aging or such diseases as diabetes mellitus (DM) and hypertension (HT). Twenty healthy male subjects (20-73 years), and 8 male patients with non-insulin-dependent DM and 8 male patients with essential HT were included in this study. A constant dose (50 ng/min) of Ang II or increasing dose (2-256 ng/min) of NA was infused into the dorsal hand vein and its diameter was measured using a linear variable differential transformer.

Impaired β-adrenoceptor mediated venodilation in patients with diabetes mellitus.

Aims We investigated whether venoconstriction by α-adrenoceptor stimulation, and venodilation by β-adrenoceptor stimulation and nitroglycerin are altered in patients with diabetes mellitus (DM). Methods Eight male patients with non insulin-dependent DM and eight age-matched control subjects were included. The patients had neither hypertension nor hyperlipidaemia.