Biomedical subjects

Brian Guth

Publications and source records attributed to Brian Guth.

4 recordsLinked to original sources

PubMed2006

Optimizing the experimental environment for dog telemetry studies.

INTRODUCTION: The objective of this study was to test the influence of housing conditions on hemodynamics during cardiovascular general pharmacological studies. Our goal was to optimize both the quality of the data through an optimization of the physiological conditions, as well as to ensure the dog's well-being in general pharmacological studies. METHODS: Two groups of four dogs were equipped with radiotelemetry transmitters and continuously monitored in two different housing models. Model I consisted of 4 cages, two on each site of a corridor. Model II consisted of 4 cages positioned in a row, where the bordering cages were not separated with a metal plate. The physiological status of the dogs in the different housing models was based on the frequency of vocalizations and the average resting heart rate, as well as video monitoring. RESULTS: The housing arrangement during the study had a remarkable effect on the hemodynamics measured. The hemodynamic parameters were best when the dogs were housed with their usual run mate. In this setting, they have impressively low average heart rates of about 60 bpm during the entire study, was associated with fewer vocalizations. DISCUSSION: This study demonstrated that the quality of the acquired cardiovascular data for conscious dogs is dependent on the pen configuration and group make-up during a study.

Animals↗

PubMed2006

Effect of commonly used vehicles on gastrointestinal, renal, and liver function in rats.

INTRODUCTION: Solubility is often a limiting factor when testing new compounds in animal experiments. Various solubilizing agents may be used, but each have their own pharmacological effects. We investigated the effects of selected vehicles having different chemical characteristics on gastrointestinal, renal, and liver function. METHODS: Rats were treated orally, intravenously or intraperitoneally and gastric emptying, intestinal transit, renal, and liver function were investigated. RESULTS: Gastrointestinal motility was influenced by hydroxyethylcellulose, hydroxypropyl-beta-cyclodextrin (HPbetaCD), HPgammaCD, DMSO, polyethylene glycol 400 (PEG 400), fat emulsion, and the corresponding emulsifier. Liver function was affected by HPbetaCD, HPgammaCD, DMSO, PEG 400, Polysorbate 80, Cremophor RH 40, and fat emulsion. An increase in liver enzymes was observed after PEG 400 and Polysorbate 80. DMSO interfered with clinical chemistry measurements in serum. Urinary function was modified by HPgammaCD, DMSO, PEG 400, and Polysorbate 80, while enhanced urine enzyme excretion was observed after HPbetaCD, HPgammaCD, DMSO, PEG 400, and Polysorbate 80. DISCUSSION: Most of the investigated vehicles changed gastrointestinal, renal, and/or liver parameters after application of a certain threshold dose for each assay. No "best" vehicle could be identified that may be used in each test system. Thus, vehicles must be selected not only on their chemical characteristics but also on their potential pharmacological activity in a given test system.

Animals↗

PubMed2004

Nonviral monocyte chemoattractant protein-1 gene transfer improves arteriogenesis after femoral artery occlusion.

Local infusion of recombinant monocyte chemoattractant protein-1 (MCP-1) has been shown to enhance collateral artery formation in rabbit and pig hindlimb models. Owing to clinical disadvantages of protein infusion, a nonviral, liposome-based MCP-1 gene transfer was developed. Collateralization in a porcine hindlimb model served to provide a proof-of-principle for the functional benefit of MCP-1 overexpression. Development of arterial conductance as a measure of functionally relevant collateralization was evaluated in occluded as well as untreated hindlimbs in each animal. At the time of occlusion, MCP-1 and control DNA/DC-30 lipoplexes were transferred to femoral arteries of Goettingen minipigs (two therapeutic MCP-1 groups: 2 and 4 microg and one control group), using the Infiltrator local drug-delivery device. At 2 weeks following occlusion, collateralization was determined as changes in peripheral haemodynamic conductance, peripheral over aortic blood pressure ratio and angiographically visible morphology of the peripheral vessel tree. Nonviral MCP-1 gene transfer significantly improved peripheral conductance (control 11.69+/-2.78%, 2 microg 23.81+/-2.81%, P<0.05 and 4 microg 23.36+/-3.1%, P<0.05; n=12 per group) as well as the ratio of peripheral over aortic blood pressure (control 0.64+/-0.03%, 2 microg 0.75+/-0.02%, P<0.05 and 4 mug 0.75+/-0.02%, P<0.05; n=12 per group) when compared to the untreated controls 2 weeks after occlusion. Thus, it could be demonstrated for the first time that in situ overexpression of MCP-1 following local nonviral gene transfer is a potential approach to improve peripheral collateralization.

Animals↗

PubMedDate not supplied

A novel propellant-free inhalation drug delivery system for cardiovascular drug safety evaluation in conscious dogs.

INTRODUCTION: Estimation of possible cardiovascular side effects belongs to the safety assessment of every drug candidate. This paper describes a new strategy for treating conscious labrador dogs with drugs by inhalation using a specially designed mask and a novel inhaler device. METHODS: Labrador dogs (male or female) were used that had transducers implanted for the measurement of left ventricular and descending aortic blood pressures and an ECG for use together with a telemetry system. Administration by inhalation was achieved using a novel delivery device. The Respimat device is a propellant-free inhaler to deliver aerosols from solutions. The new system was evaluated using Formoterol with four dogs using a 4 x 4 Latin square design. Three doses of Formoterol (0.6, 1.2, and 2.4 microg/kg, dissolved in 60% ethanol) were administered by inhalation together with a vehicle (60% ethanol) treatment by applying three inhalations, each consisting of 10 microl solution. RESULTS: Formoterol increased HR, QRS-interval, QT-interval, and LVPdP/dtmax and dose-dependently decreased systolic and diastolic BP. This effect lasted up to 14 h. DISCUSSION: Drug administration by inhalation in the conscious labrador dog using the Respimat is a useful new model for safety pharmacology studies of new drug candidates that are intended to be given by inhalation in the clinic.

Administration, Inhalation↗