Frank L. Douglas

Magnetic resonance imaging reflects cartilage proteoglycan degradation in the rabbit knee

Cartilage degeneration in osteoarthritis is initiated by a loss of proteoglycan. Intra-articular injection of papain causes a reversible loss of proteoglycan in rabbit knees. Rabbits were scanned with magnetic resonance imaging (MRI), using a 1.5T Signa superconducting magnet with 3 inch surface coil. Spin echo sequences were performed in the coronal and sagittal planes at 0, 24, 48, and 72 h after intra-articular injection of papain to obtain T1, proton density, and T2-weighted images. Cartilage proteoglycan content was measured biochemically and histochemically. Reduced articular cartilage thickness in the MR images of papain-treated knees corresponded to changes in cartilage proteoglycan content.

Increased blood-brain barrier permeability of amino acids in chronic hypertension

A previous communication from this laboratory reported that brain uptake of libenzapril, a small polar molecule, was enhanced in chronic hypertension (1). The objective of this investigation was to determine if this was a more generalized phenomenon. Therefore, experiments were undertaken to examine the effect of chronic hypertension on the brain uptake of tryptophan (an amino acid with high brain permeability) and glutamic acid (one with low permeability). Brain concentrations of these two amino acids were 5- to 12-fold greater in chronic hypertensive rats, as compared to normotensive rats; the corresponding brain uptake index (BUI) values were 2- to 5-fold higher in the former group. Since blood-brain barrier transport of amino acids involve both saturable (carrier) and non-saturable (most likely, diffusion via pores) mechanisms, data from this study show that hypertension can enhance BBB transport of amino acids by affecting one or both of these pathways.

Magnetic resonance imaging of the rabbit knee: Detection of cartilage proteoglycan degradation

Intra-articular (i.a.) injection of papain causes a reversible loss of proteoglycan in intact rabbit knees. Twelve rabbits were scanned with magnetic resonance imaging (MRI) at 0, 24, 48 and 72 hours after 5 units of papain i.a. in a 1.5 Tesla Signa with a three inch surface coil using spin echo sequence. Total cartilage thickness in proton density images was 1.08±0.09 mm prior to papain injection. The magnetic resonance images showed a reduction in articular cartilage thickness in papain-treated rabbit femurs at 24 hours to 0.69±0.18 mm and partial restoration by 72 hours to 0.77±0.21 mm.

MRI evaluation of left ventricular hypertrophy in a canine model of aortic stenosis.

The progression of ventricular myocardial mass in nine puppies with experimental left ventricular hypertrophy and three controls was observed over a period of 7 months using magnetic resonance imaging (MRI). Left ventricular hypertrophy was created by surgically induced aortic stenosis when the puppies were 1 month old. Quantification of the progression of the left ventricular mass due to aortic stenosis as compared to the controls of similar age was then performed during the subsequent 7 months. Cardiac gated spin-echo technique was used for the imaging of the heart. Novel edge detection techniques were applied for automated identification of the border of the myocardium for measurement. Methods for correction of partial volume effect were applied in the analysis of the data. Clear-cut differences in myocardial mass (P less than .001) and in radius-to-wall thickness ratio (r/h, P less than .02) between puppies with aortic stenosis and controls were observed. The differences in end-diastolic volume between the two groups, however, were significant during the initial phase of hypertrophic compensation (P less than .001) and insignificant (P greater than .05) during the long-term phase of hypertrophic compensation. The results demonstrated that MRI is applicable in serial assessment of myocardial hypertrophy.

Effect of Chronic Hypertension on the Blood–Brain Barrier Permeability of Libenzapril

AbstractVery little information is available on the permeability of theblood–brain barrier (BBB) to small polar drugs inchronic hypertension. The blood and cerebrospinal fluid (CSF)pharmacokinetics of liben-zapril (LZP), a potentangiotensin converting enzyme inhibitor, were investigated inhypertensive (SH) and normotensive (SD) rats.Following intravenous bolus administration of this hydrophilic drug, theterminal rate constant for elimination (β),steady-state volume of distribution (

Pharmacokinetic screening of o-naphthoquinone 5-lipoxygenase inhibitors.

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Inhibition of cholera-toxin-stimulated intestinal secretion by CGS 9343B in rats: a specific calmodulin inhibitor.

), and systemic clearance (CL) were similar in these two animalgroups. Other pharmacokinetic parameters (Cp°,α, kl2, and k21)were significantly (P < 0.05) greater in thehypertensive group, except for the volume of the central compartment(Vc) and ratio of Vc to