Mg2+ efflux from the isolated perfused rabbit heart is mediated by two states of the beta1-adrenergic receptor.

The non-selective beta-adrenergic receptor agonist isoproterenol stimulates Mg(2+) efflux from the perfused heart. The beta-adrenergic receptor subtype governing Mg(2+) efflux was determined in rabbit hearts perfused by the method of Langendorff with Mg(2+)-free Krebs Henseleit buffer. Magnesium efflux was examined during infusion of isoproterenol (a non-selective beta-adrenergic agonist), dobutamine (beta(1)-selective), salbutamol (beta(2)-selective), BRL37344 in the presence of 200 nM propranolol (beta(3)-selective conditions) or CGP12177 (beta(3)/low affinity state beta(1)-selective).

Comparison of the stabilities and unfolding pathways of human apolipoprotein E isoforms by differential scanning calorimetry and circular dichroism.

Differential scanning calorimetry and circular dichroism experiments were performed to study structural differences among the common isoforms of human apolipoprotein E (apoE2, apoE3, and apoE4) and their N-terminal, 22-kDa fragments. Here, we examine thermodynamic properties that characterize the structural differences among isoforms, and also differences in their unfolding behavior. The 22-kDa fragments and their full-length counterparts were found to exhibit similar differences in thermal stability (apoE4 View Article and Find Full Text PDF

Synthetic cervical mucus formulation.

A synthetic formulation has been developed with viscosity, spinnbarkeit, and pH comparable to that reported for human cervical mucus. The formulation contains guar gum crosslinked with borate ion, mucin (dried porcine gastric), and a mixed preservative system in pH 7.4, 0.

Antimicrobial diterpenes from the stem bark of Mitrephora celebica.

Four diterpenes were isolated from the stem bark of Mitrephora celebica through bioassay-guided fractionation. Ent-trachyloban-19-oic acid (1) and ent-kaur-16-en-19-oic acid (2) were identified as the compounds responsible for the antimicrobial activity of the plant against methicillin-resistant Staphylococcus aureus and Mycobacterium smegmatis. 8(14),15-pimaradien-18-oic acid (3) and 7,15-pimaradien-18-oic acid (4) were isolated from the same fraction and were inactive against the microorganisms.

Evaluation criteria for pharmacoeconomic and health economic Internet resources.

The purpose of this paper is to present criteria for evaluating Internet sites and supply a selective sample of sites that may be useful in improving the transfer of information and diffusion of innovation in pharmacoeconomics and health economics. The nine criteria deal with the following: 1) Expertise - Qualified individuals should generate the information. 2) Confidentiality - All patient data should be confidential and protected.

Comparison of contact lens multipurpose solutions by in vitro sodium fluorescein permeability assay.

Purpose: This article reports the use of in vitro sodium fluorescein permeability assay to study the effects of various contact lens disinfecting solutions on the integrity of epithelium.

Methods: We compared the sodium fluorescein permeability of monolayer cultures of Madin-Darby canine kidney cells (MDCK) after exposure to ReNu Multi-Purpose Solution, ReNu MultiPlus Multi-Purpose Solution, OPTIFREE Express Multi-Purpose Solution, OPTIFREE Express Solution with Aldox, SOLO-care Solution and Complete Comfort Plus Solution. Additional cell monolayer inserts were prepared for each treatment and were analyzed using a scanning electron microscope.

An adjusted pharmacokinetic equation for predicting drug levels in vivo based on in vitro square root of time release kinetics.

An adjusted pharmacokinetic equation that predicts in vivo plasma drug profiles for controlled release (CR) dosage forms having square root of time drug release kinetics has been derived. The CR hydrogel tablets containing hydroxypropyl methylcellulose (HPMC) were formulated with theophylline and Fast Flo lactose, to produce tablets with HPMC K100MP content of 30% w/w. Plasma profiles in vivo were determined from four male beagle dogs.

The effect of controlled release tablet performance and hydrogel strength on in vitro/in vivo correlation.

The impact of controlled release (CR) formulations having different gel strength values (gamma) on in vivo tablet performance and the in vitro/in vivo correlation of the formulations was investigated. The CR tablets containing either hydroxypropyl methylcellulose (HPMC), hydroxypropyl cellulose (HPC), or carbomer were formulated with theophylline and Fast Flo lactose to produce tablets with a polymer content of 8 and 30% w/w. gamma was measured using a previously reported method.

Conditioned inhibition of cyclophosphamide-induced taste aversion.

Rats in an experimental group received trials during which 1 flavor (saccharin) was always followed by cyclophosphamide, an immunosuppressive drug, but another (vanilla) was not. An unconditioned stimulus-only group served as a control. Flavor-preference tests revealed that conditioned excitation and conditioned inhibition occurred in the conditioned group subjects but not in the control group subjects.

Racemic salbutamol administration to guinea-pigs selectively augments airway smooth muscle responsiveness to cholinoceptor agonists.

1. An aim of this study was to investigate whether continuous in vivo administration of a low dose of salbutamol to guinea-pigs alters the responsiveness of airway smooth muscle in vitro. 2.

Nontraditional dosing of ampicillin-sulbactam for multidrug-resistant Acinetobacter baumannii meningitis.

A 52-year-old man was admitted to a local hospital with headache, nausea, vomiting, dizziness, photophobia, and confusion after a sudden fall. Progressive changes in neurologic function were noted despite neurosurgical intervention and broad-spectrum antimicrobial coverage. Cerebral spinal fluid (CSF) culture identified Acinetobacter baumannii that was resistant to traditionally recommended therapies of amikacin and imipenem-cilastatin.

Removal of lepirudin, a recombinant hirudin, by hemodialysis, hemofiltration, or plasmapheresis.

Lepirudin (recombinant hirudin), a direct thrombin inhibitor, is an effective alternative method of anticoagulation in patients with heparin-induced thrombocytopenia. However, because it is eliminated by the kidneys, the half-life of lepirudin may be substantially prolonged in patients with renal failure. Patients undergoing hemodialysis must be closely monitored, and therapy must be individualized based on each patient's ability to clear the drug.

New drugs of 2001.

Objective: To provide information regarding the most important properties of the new therapeutic agents marketed in 2001.

Data Sources: Published studies, drug information reference sources, and product labeling.

Data Synthesis: In 2001, 26 new therapeutic agents were marketed.

Clinical observations with the amiodarone/warfarin interaction: dosing relationships with long-term therapy.

Objectives: The interaction between amiodarone and warfarin has only been described in patients being followed up for relatively short time periods. The objectives of this study were to characterize the interaction between these two agents in a clinical situation over a longer period of time in a larger cohort of patients, and to determine the relationship between the maintenance dose of amiodarone and the resultant need to adjust the dose of warfarin.

Design: This was an observational trial of a cohort of patients receiving a stable warfarin regimen in whom oral amiodarone was initiated.

Renal damage, metabolism and covalent binding following administration of the nephrotoxicant N-(3,5-dichlorophenyl)succinimide (NDPS) to male Fischer 344 rats.

In vivo metabolism, nephrotoxicity and covalent binding to proteins were evaluated in male Fischer 344 rats that received [2,3-14C]-N-(3,5-dichlorophenyl)succinimide (14C-NDPS). Some animals were pretreated with the enzyme inducer phenobarbital (PB, 80 mg/kg per day, for 3 days, i.p.

The effect of formulation composition and dissolution parameters on the gel strength of controlled release hydrogel tablets.

The impact of hydrogel polymers and dissolution media on tablet gel strength, Gamma, of controlled release (CR) hydrogel tablets was investigated. CR tablets containing either hydroxypropyl methylcellulose (HPMC), hydroxypropyl cellulose (HPC), or carbomer were formulated with theophylline and Fast Flo lactose, to produce tablets with a polymer content of 8, 15, and 30% w/w. Gamma was measured using a previously reported method.

The effects of formulation factors on the moist granulation technique for controlled-release tablets.

Controlled-release tablets were prepared by the moist granulation technique (MGT), a granulating method that uses very limited amounts of liquid and requires microcrystalline cellulose (MCC) to absorb moisture. Acetaminophen (APAP) was the model drug, and the polymer hydroxypropylcellulose (HPC) served as the controlled-release agent. The effects of varying drug, binder (polyvinylpyrrolidone, PVP), polymer, and MCC levels on granule properties and tablet dissolution were studied.

Measuring reliability of effort in functional capacity evaluations using digital video analysis.

Functional capacity evaluations (FCE) are utilized to evaluate the physical abilities of workers to perform the specific demands of a job. FCEs are being used increasingly by insurers, employers, health care providers and attorneys as the basis to make decisions regarding workplace supports, vocational rehabilitation, disability determination, and litigation. These factors require that FCEs must have objectivity, reliability, validity and defensibility.

Derivation of 13C chemical shift surfaces for the anomeric carbons of oligosaccharides and glycopeptides using ab initio methodology.

The dependence between the anomeric carbon chemical shift and the glycosidic bond (phi, psi) dihedral angles in oligosaccharide and glycopeptide model compounds was studied by Gauge-Including Atomic Orbital (GIAO) ab initio calculations. Complete chemical shift surfaces versus phi and psi for D-Glcp-D-Glcp disaccharides with (1-->1), (1-->2), (1-->3), and (1-->4) linkages in both alpha- and beta-configurations were computed using a 3-21G basis set, and scaled to reference results from calculations at the 6-311G** level of theory. Similar surfaces were obtained for GlcNAcThr and GlcNAcSer model glycopeptides in alpha- and beta-configurations, using in this case different conformations for the peptide moiety.

Polyacetylene carboxylic acids from Mitrephora celebica.

A new polyacetylene carboxylic acid, 13(E),17-octadecadiene-9,11-diynoic acid (13,14-dihydrooropheic acid, 1), and the known 17-octadecene-9,11,13-triynoic acid (oropheic acid, 2) were isolated from the stem bark of Mitrephora celebica through bioassay-guided fractionation. Both compounds demonstrated significant activity against methicillin-resistant Staphylococcus aureus and Mycobacterium smegmatis.

Risedronate: a new oral bisphosphonate.

Background: Bisphosphonates have been effective in the treatment of osteoporosis and Paget's disease of bone. Risedronate, the newest oral bisphosphonate, is approved by the US Food and Drug Administration for the prevention and treatment of postmenopausal osteoporosis and glucocorticoid-induced osteoporosis and the treatment of Paget's disease of bone.

Objective: This article reviews current studies of risedronate in osteoporosis and Paget's disease of bone and, to the extent possible, compares risedronate with other bisphosphonates and other therapies.