Potentiation of carbon monoxide-induced relaxation of rat aorta by YC-1 [3-(5'-hydroxymethyl-2'-furyl)-1-benzylindazole].

The hypothesis that endogenous carbon monoxide (CO), produced during the oxidation of heme catalyzed by heme oxygenase (HO), plays a role similar to that of nitric oxide (NO) in the regulation of cardiovascular tone has been criticized because of the low potency of CO compared with NO in relaxing blood vessels and stimulating soluble guanylyl cyclase (sGC). This criticism has been muted by the demonstration that, in the presence of YC-1 [3-(5'-hydroxymethyl-2'-furyl)-1-benzylindazole], CO has similar potency to NO in stimulating sGC activity. In this study, we determined that YC-1 potentiated CO-induced relaxation of rat aortic strips (RtAS) by approximately ten-fold.

Chronic ethanol exposure during late gestation produces behavioral anomalies in neonatal lambs.

A total of 45 pregnant ewes were assigned to one of three treatment groups: 1 g ethanol/kg maternal body weight (n = 18); pair-fed control (n = 15); and ad lib control (n = 12). Dosing started at gestational day (GD) 106, and was administered every other day until GD 134. Parturition occurred between GD 144 and 147.

Effects of chronic prenatal ethanol exposure on locomotor activity, and hippocampal weight, neurons, and nitric oxide synthase activity of the young postnatal guinea pig.

Decreased nitric oxide synthase (NOS)-catalyzed formation of NO from L-arginine may be involved in ethanol teratogenesis involving the hippocampus. This hypothesis was tested by determining the effects of chronic prenatal ethanol exposure on locomotor activity and on hippocampal weight, number of CA1 and CA3 pyramidal cells and dentate gyrus granule cells, and NOS activity of the postnatal guinea pig. Timed, pregnant guinea pigs received one of the following chronic oral regimens throughout gestation: 4 g ethanol/kg maternal body weight/day, isocaloric-sucrose/pair-feeding, or water.

Altered GABA(A)-benzodiazepine receptor number and pharmacology in the adult guinea pig cerebral cortex after chronic prenatal ethanol exposure.

Background: The effects of chronic prenatal ethanol exposure on GABA(A)-benzodiazepine receptor number and binding pharmacology were examined in the cerebral cortex of the postnatal guinea pig.

Methods: [3H]Flunitrazepam binding to GABA(A)-benzodiazepine receptors was measured in a cerebral cortical cell membrane preparation obtained at postnatal days 11 (preweaning), 21 (postweaning), and 61 (adulthood). Zolpidem, a GABA(A)-benzodiazepine type 1 receptor-selective ligand, was used in a [3H]flunitrazepam competition study.

Ontogeny of nitric oxide synthase I and III protein expression and enzymatic activity in the guinea pig hippocampus.

60. NOS enzymatic activity increased throughout prenatal and postnatal life, and attained highest activity in the adult. The developmental profile of NOS III protein expression was similar to that for NOS enzymatic activity.

The adenosine A(1)-receptor antagonist 8-CPT reverses ethanol-induced inhibition of fetal breathing movements.

Administration of either ethanol or adenosine inhibits fetal breathing movements (FBM), eye movements, and low-voltage electrocortical activity (LV ECoG). The concentration of adenosine in ovine fetal cerebral extracellular fluid increases during ethanol-induced inhibition of FBM. The purpose of this study was to determine the effect of a selective adenosine A(1)-receptor antagonist, 8-cyclopentyltheophylline (8-CPT) on the incidence of FBM during ethanol exposure.

Selective inhibition of heme oxygenase, without inhibition of nitric oxide synthase or soluble guanylyl cyclase, by metalloporphyrins at low concentrations.

Studies on the physiological role of heme oxygenase (HO) require an inhibitor that will selectively inhibit HO activity without inhibiting the activity of either nitric oxide synthase (NOS) or soluble guanylyl cyclase (sGC). The objective of this study was to test a series of metalloporphyrins that have previously been shown to inhibit HO activity, for their ability to inhibit HO without inhibiting NOS or sGC activities. Measurement of activity of HO in rat brain microsomes and NOS in rat brain cytosol was made for samples incubated with metalloporphyrins (0.

Assessing patient satisfaction across the continuum of ambulatory care: a revalidation and validation of care-specific surveys.

The need to develop reliable and valid measures of patient satisfaction in ambulatory care settings is underscored by the rapid growth and changes in this health care arena as well as the requirement to monitor and gauge quality of care. The purpose of this article is to provide evidence for the reliability and validity of patient satisfaction questionnaires designed specifically for three points of care across the ambulatory care continuum. These points are outpatient testing and physical therapy services, outpatient surgery, and home health care.

Effect of chronic prenatal ethanol exposure on nitric oxide synthase I and III proteins in the hippocampus of the near-term fetal guinea pig.

Chronic prenatal ethanol exposure suppresses nitric oxide synthase (NOS) enzymatic activity, in the hippocampus of the near-term fetal guinea pig at gestational day (GD) 62. The objective of this study was to determine if this decrease in NOS activity is the result of decreased NOS I and NOS III protein expression. Pregnant guinea pigs received oral administration of 4 g ethanol/kg maternal body weight/day (n = 8), isocaloric-sucrose/pair feeding (n = 8), or water (n = 8) from GD 2 to GD 61.

Effects of dietary vitamin E supplementation on pulmonary morphology and collagen deposition in amiodarone- and vehicle-treated hamsters.

Amiodarone (AM) is a potent antidysrhythmic agent that is limited in clinical use by its adverse effects, including potentially life-threatening AM-induced pulmonary toxicity (AIPT). The present study tested the ability of dietary supplementation with vitamin E (500 IU d,1-alpha-tocopherol acetate/kg chow) to protect against pulmonary damage following intratracheal administration of AM (1.83 micromol) to the male golden Syrian hamster.

Chronic ethanol exposure alters MK-801 binding sites in the cerebral cortex of the near-term fetal guinea pig.

The mechanism of ethanol central nervous system (CNS) teratogenesis, resulting from chronic maternal ingestion of high-dose ethanol during pregnancy, is not clearly understood. One of the target sites for ethanol-induced damage in the developing brain is the cerebral cortex. It has been proposed that chronic prenatal ethanol exposure alters NMDA receptors in the developing cerebral cortex.

Glyceryl trinitrate-induced vasodilation is inhibited by ultraviolet irradiation despite enhanced nitric oxide generation: evidence for formation of a nitric oxide conjugate.

Our objective was to determine whether a stabilized form of nitric oxide (NO) such as an S-nitrosothiol, rather than NO itself, is the vasoactive metabolite produced when glyceryl trinitrate (GTN) interacts with vascular smooth muscle. In a control study, NO formation was measured by a chemiluminescence-headspace gas method during the incubation of a prototype S-nitrosothiol, namely, S-nitroso-N-acetylpenicillamine (SNAP), in Krebs' solution. NO formation from SNAP was increased when the incubation was carried out in the presence of UV light, indicating that homolytic photolysis of the S-nitrosothiol had occurred.

Increased cerebral extracellular adenosine and decreased PGE2 during ethanol-induced inhibition of FBM.

Adenosine and PGE2 are neuromodulators, both of which inhibit fetal breathing movements (FBM). Although circulating PGE2 has been implicated as a mediator of ethanol-induced inhibition of FBM in the late-gestation ovine fetus, a role for adenosine has not been examined. The objective of this study was to determine the effect of maternal ethanol infusion on ovine fetal cerebral extracellular fluid adenosine and PGE2 concentrations by using in utero microdialysis and to relate any changes to ethanol-induced inhibition of FBM.

Neurosteroid modulation of the GABAA receptor in the developing guinea pig cerebral cortex.

Developmental changes in 5alpha-pregnan-3alpha-ol-20-one (allopregnanolone; 5alpha-3alpha-P) potentiation of muscimol and benzodiazepine binding to the GABAA receptor were studied in the guinea pig cerebral cortex at three prenatal ages (gestational day (GD) 40, GD 50, GD 62), and three postnatal ages (postnatal day (PD) 11, PD 21, PD 61) (term, about GD 68). The number and affinity of [3H]flunitrazepam binding sites, and 5alpha-3alpha-P potentiation of [3H]muscimol and [3H]flunitrazepam binding to the GABAA receptor were determined at each age. There was no age effect on the affinity (Kd) for [3H]flunitrazepam.

Differential susceptibilities of isolated hamster lung cell types to amiodarone toxicity.

Treatment of cardiac dysrhythmias with the iodinated benzofuran derivative amiodarone (AM) is limited by pulmonary toxicity. The susceptibilities of different lung cell types of male Golden Syrian hamsters to AM-induced cytotoxicity were investigated in vitro. Bronchoalveolar lavage and protease digestion to release cells, followed by centrifugal elutriation and density gradient centrifugation, resulted in preparations enriched with alveolar macrophages (98%), alveolar type II cells (75-85%), and nonciliated bronchiolar epithelial (Clara) cells (35-50%).

Analysis of nanomolar S-nitrosothiol concentrations in physiological media.

S-Nitrosothiols occur endogenously and are thought to function as storage forms and/or stable carriers of nitric oxide. Moreover, the S-nitrosothiols have been postulated to function as neurotransmitters and mediate the vasodilator action of glyceryl trinitrate. Because of the increasing pharmacological and physiological interest in S-nitrosothiols, a sensitive method for analysis of these substances is required.

Relationships among liver and kidney volumes, lean body mass and drug clearance.

Aims: To determine whether lean body mass (LBM), a possible surrogate of liver and kidney volumes, correlates with hepatic and renal drug clearances.

Methods: Twenty-one disease-free patients with a history of cancer and with normal hepatic and renal function were studied. Salivary pharmacokinetics of oral antipyrine (1200 mg) and 24 h creatinine clearance were determined following the determination of LBM by dual energy X-ray absorptiometry and the determination of liver and kidney volumes by helical CT scanning.

The incidence of drug-related problems as a cause of hospital admissions in children.

Objectives: To determine the incidence of hospital admissions for drug-related problems (DRPs) among children, and to examine cases for causality, preventability and clinical severity.

Design: Prospective assessment involving review of case notes and parent interview to determine if an admission was associated with a DRP.

Patients And Setting: All patients admitted to a large university-affiliated paediatric hospital in Melbourne, Victoria, for medical reasons (i.

Heme oxygenase and nitric oxide synthase in the placenta of the guinea-pig during gestation.

Nitric oxide (NO) and carbon monoxide (CO) are novel gaseous chemical messengers that play key roles in cell function and cell-cell communication in many organ systems, including the cardiovascular system. Although the presence of NO synthase (NOS) in the placenta and its role in the regulation of fetoplacental and uteroplacental blood flow are well established, little is known about placental expression and activity of heme oxygenase (HO), the enzyme that catalyses the oxidation of heme to CO, biliverdin and iron, during gestation. The objectives of this study were to elucidate the localization of HO-1 and HO-2 isoforms relative to NOS III protein, and to determine the enzymatic activity of HO in the placenta of the guinea-pig during gestation.

Amiodarone-induced disruption of hamster lung and liver mitochondrial function: lack of association with thiobarbituric acid-reactive substance production.

Amiodarone (AM) is an efficacious antidysrhythmic agent that is limited clinically by numerous adverse effects. Of greatest concern is AM-induced pulmonary toxicity (AIPT) due to the potential for mortality. Mitochondrial alterations and free radicals have been implicated in the etiology of AM-induced toxicities, including AIPT.

Use of nitroglycerin for uterine relaxation.

Data from human and experimental animal research indicate that nitric oxide (NO), a novel messenger, formed during the nitric oxide synthase-catalyzed oxidation of L-arginine to L-citrulline, is involved in maintaining normal uterine tone during gestation. There are demonstrated and potential benefits of manipulating the L-arginine-NO system during pregnancy. Several recent case reports and case series have described the effective use of nitroglycerin (GTN), a NO donor compound, antenatally, intrapartum, and postpartum for acute uterine relaxation.

Nitrate and nitrite anion concentration in the intact cerebral cortex of preterm and nearterm fetal sheep: indirect index of in vivo nitric oxide formation.

Pregnant sheep with a microdialysis probe implanted in the fetal cerebral cortex were used to determine if nitrate and nitrite anions (nitrate/nitrite) could be quantitated in the microdialysate as an indirect index of in vivo nitric oxide formation. Pregnant ewes (term, about 147 days) were surgically instrumented at gestational day (GD) 90 (n = 3; preterm) and GD 121 (n = 3; nearterm). Three days later, following an overnight probe equilibration period, five dialysate samples were collected continuously on ice at 1-h intervals (infusion rate of 1 (microl/min).

Thiol agents separate nitric oxide formation from vasodilation induced by glyceryl trinitrate.

The role of nitric oxide (NO) and thiol-containing compounds in glyceryl trinitrate (GTN)-induced vasodilation was investigated using the thiol-alkylating agent N-ethylmaleimide (NEM). Bovine pulmonary artery (BPA) rings were submaximally contracted with K+ and exposed to increasing concentrations of GTN after a 30-min incubation with 50 microM NEM. NEM decreased maximal relaxation (10 microM GTN) by 20%, compared with controls.

Initial concentration-time profile of gentamicin determines efficacy against Enterobacter cloacae ATCC 13047.

In vitro studies were designed to investigate the influence of peak drug concentration (Cmax), the area under the concentration-time curve (AUC), and, consequently, the trough concentration on the bactericidal effects of gentamicin against Enterobacter cloacae (MIC, 0.5 mg/liter) by simulating bolus versus infusion administration and bolus dosing with altered drug clearance. Bacteria in the lag phase were exposed to gentamicin concentration-time profiles modelling either bolus or infusion dosing (AUC constant, Cmax changing) with 30-min postdose peak concentrations (Cpeak30) of 4, 6, 8, and 10 mg/liter or bolus dosing with normal and double drug clearance (Cmax constant, AUC changing) corresponding to normal clearance profiles with Cpeak30 of 6 and 8 mg/liter.

Hippocampal nitric oxide synthase in the fetal guinea pig: effects of chronic prenatal ethanol exposure.

The effects of chronic maternal administration of ethanol on nitric oxide synthase (NOS) activity and the numbers of NOS containing neurons, and CA1 and CA3 pyramidal neurons in the hippocampus of the near term fetal guinea pig at gestational day (GD) 62 were investigated. Pregnant guinea pigs received oral administration of 4 g ethanol/kg maternal body weight (n = 5), isocaloric sucrose/pair feeding (n = 5) or water (n = 5), or no treatment (NT; n = 5) from GD 2 to GD 61. NOS activity in the 25,000 x g supernatant of hippocampal homogenate was determined using a radiometric assay.