Experimental lead arthropathy: an animal model.

BACKGROUND: We previously demonstrated short-term effects of intra-articular lead on joint structures in an animal model. We now present histopathologic findings in animals studied over a more extended period. METHODS: Twelve female New Zealand White rabbits had identical lead or stainless steel pellets, or a sham arthrotomy (without implant) inserted in both front knees. The rabbits were killed 4 at a time at 6, 10, and 14 weeks after implantation, and the knee joint structures were evaluated histologically for changes in the synovium, articular cartilage, and meniscus. RESULTS: Histology of the tibial articular surface, femoral articular surface, medial meniscus, lateral meniscus, and synovium showed greater signs of degeneration in the knees with lead implants than controls at all time periods. CONCLUSION: Intrasynovial lead, which does not undergo fibrous encapsulation, has been linked to lead intoxication. Clinical and experimental reports support removal of lead bodies from articular areas in an attempt reduce or slow the degeneration of affected joints. Nonmechanical effects of lead on intraarticular structures may lead to degenerative changes

Atriopeptin does not augment the transvascular flux of macromolecules in the hamster cheek pouch.

Natriuretic peptides elaborated by atrial myocytes promote marked renal sodium and water excretion as a mechanism for fluid and electrolyte balance. Recent evidence suggests that atriopeptin (ANP) also targets the non-renal vasculature as a site for enhanced fluid exchange. It remains unclear whether ANP alters microvascular integrity to facilitate the efflux of both plasma and proteins across the endothelial barrier, or if fluid exchange is selectively enhanced. This study evaluated the influence of ANP on macromolecular transport through the direct observation of microvessels in the hamster cheek pouch using fluorescent intravital microscopy. Fluorescein isothiocyanate conjugated to either bovine serum albumin or dextran 150,000 Mw was utilized as a permeability probe. Macromolecular efflux was quantified as fluorochrome clearance. The clearance of fluorescein-conjugated bovine serum albumin (57.94 +/- 7.03) or fluorescein-conjugated dextran 150 (4.09 +/- 1.35) remained unaltered by intravascular injection of 1 microgram/kg ANP. Topical application of 40 ng to cheek pouch microvessels produced similar results. All pouches demonstrated positive leakage response to histamine 2.5 x 10(-6) M, increasing fluorochrome clearance approximately 2- to 11-fold. Bolus injection of 1 microgram/kg ANP reduced mean arterial pressure, increased urine flow from 6.63 +/- 2.59 microliters/min to 8.20 +/- 6.13 microliters/min, and elevated sodium excretion from 1.37 +/- 0.49 microEq/min to 2.54 +/- 0.99 microEq/min. These results suggest that ANP fails to significantly alter the integrity of the protein-transporting channels in the microvascular exchange barrier.

Leukocyte phagocytosis and alterations in microvascular integrity elicited by FITC-dextran 150 and epi-illumination in the microcirculation of the hamster cheek pouch.

Fluorescein-labeled dextran MW 150K (FITC-Dx 150) is commonly utilized as a macromolecular fluorochrome in inflammatory studies. We examined the influence of FITC-Dx 150 on leukocyte activity as assessed by adherence to cheek pouch microvessels. Transcapillary exchange was evaluated as fluorochrome clearance (Cl). Few leukocytes adhered to the microvascular wall in venous segments prior to and immediately following administration of the dextran fluorochrome. Spontaneous leukocyte adhesion to venous endothelium ensued within 30 min in epi-illuminated, FITC-Dx 150-loaded vessels. However, the Cl of FITC-Dx 150 (1.75 +/- 0.68 nl/min) remained unaltered (2.21 +/- 1.83 nl/min). Hamsters pretreated with FITC-Dx 150 (a minimum of 7 hr prior to experimentation) and subsequently exposed to epi-illumination showed marked leukocyte adhesion in small venules and an impressive pool of marginating leukocytes in large venules. Leukocyte aggregation, thrombus formation, lymphatic distension, and leukocyte adherence to arteriolar endothelium also ensued as a consequence of epi-illumination. Uptake of FITC-Dx 150 by extravascular phagocytes was evident. Some hamsters pretreated with FITC-Dx 150 developed spontaneous leaky sites upon epifluorescent stimulation. Focal accumulation of interstitial phagocytes was suggestive of fluorochrome uptake and elicitation by FITC-Dx 150. These effects were not observed in control animals treated with FITC-albumin. The results of this study suggest caution in employing FITC-Dx 150 as a permeability probe for studies involving inflammatory processes, especially those dependent on neutrophil/endothelial interactions and prolonged circulation time of fluorochrome.

cis-Flupentixol antagonism of the rat prefrontal cortex neuronal response to apomorphine and ventral tegmental area input.

This study was designed to characterize the response of a select population of prefrontal cortex neurons to exogenous and endogenous dopaminergic influences. Of particular interest were neurons with efferent projections to the ventral tegmental area (VTA) which are part of a reciprocal innervation between the prefrontal cortex and the VTA. Extracellular single unit recording techniques were used to determine the response of cortical neurons to electrical stimulation of the VTA in chloral hydrate anesthetized rats. The neurons were selected on the basis of their electrophysiological characteristics (large amplitude with positive initial deflection) and were classified as to whether or not they were antidromically activated from the VTA. Apomorphine (25 micrograms/kg, IV) significantly reduced the spontaneous activity of both the antidromically identified and the unidentified prefrontal cortex neurons. The apomorphine (25 micrograms/kg, IV) response was antagonized by cis-flupentixol (1.0 mg/kg, IV) in both antidromically identified and unidentified cortical neurons. Stimulation of the VTA also induced a synaptically mediated inhibition of the cortical neuron spontaneous activity. The orthodromic VTA stimulus-evoked inhibition was antagonized by cis-flupentixol (1.0 mg/kg, IV) for both the antidromically identified and the unidentified neurons (63 and 71% of the neurons respectively). The results indicate that a select population of prefrontal cortex neurons respond specifically to exogenous and endogenous dopaminergic influences and that the response is independent of efferent projections to the VTA.