Bile salt-induced injury of rabbit oesophageal mucosa measured by hydrogen ion disappearance

Oesophageal injury secondary to gastro-oesophageal reflux is unlikely to be due to the effects of hydrochloric acid alone. The present authors have investigated the development of acid and bile salt-induced oesophageal mucosal injury in a rabbit model. Solutions of hydrochloric acid and sodium taurocholate (ST) were perfused through an isolated oesophageal preparation and mucosal injury was determined by measuring the rate of H+ disappearance. Perfusion with acid alone in concentrations up to 10 mmol/l did not affect the H+ disappearance rate. Addition of 1 mmol/l ST to an acid perfusate resulted in loss of H+ from the system. The increase in H+ disappearance rate was associated with loss of ST from the perfusate. Sodium taurocholate was only lost from the system when in an acid medium. Increased rate of H+ disappearance occurred even after the bile salt had been washed out of the perfused oesophagus. The mechanism of bile salt-induced mucosal injury was unlikely to be due to mucosal disruption secondary to micelle formation since the critical micellar concentration of taurocholate was found to be greater than that used in the perfusate. These findings indicate that bile salts may be an important factor in hydrochloric acid-related damage to oesophageal mucosa, by acting through mechanisms unrelated to micelle formation.     

Differential distribution of growth associated protein (GAP-43) in the motor nuclei of the adult rat conus medullaris

GAP-43 is normally produced by neurons during developmental growth and axonal regeneration, but it is also expressed in specific regions of the normal adult nervous system. We studied the protein expression of GAP-43 within the conus medullaris portion of the spinal cord in adult male rats. Immunohistochemistry for choline acetyltransferase (ChAT) was first performed to identify specific efferent autonomic and motor nuclei in lumbosacral segments of the spinal cord. Adjacent sections were then processed for GAP-43 immunoreactivity (IR). We show GAP-43 IR in the superficial portion of the dorsal horn, the intermediolateral nucleus, and the dorsal commissural tract. We also demonstrate a differential distribution of GAP-43 IR between different motor nuclei of the conus medullaris. Using densitometry, the most prominent GAP-43 IR was detected in the dorsolateral and dorsomedial motor nuclei, which represent the human Onufs nucleus homologue. Confocal microscopy of double immunofluorescent labeling for ChAT and GAP-43 demonstrate GAP-43 IR in the neuropil of the autonomic and motor nuclei, and many of the GAP-43 IR arbors are in close apposition with the efferent cholinergic neurons. We note that the efferent neurons of both the autonomic and somatic nuclei, which are ultimately responsible for the integrated normal control of the lower urinary tract, bowel and sexual functions, are heavily innervated by GAP-43 enriched projections. We speculate that these functionally related neurons retain a physiological GAP-43-associated synaptic plasticity throughout adult life.     

Paramagnetic macrocyclic complexes as contrast agents for MR imaging: proton nuclear relaxation rate enhancement in aqueous solution and in rat tissues

Paramagnetic macrocyclic chelates show promise as magnetic resonance (MR) imaging contrast agents due to stability and relaxivity comparable to those of DTPA-type chelates. For the three copper and manganese macrocyclic complexes studied in aqueous solution, T1 and T2 relaxivities ranged from 0.14 to 5.88 mM-1sec-1 at 6.25 MHz. In rats, the intravenous administration of 16 mumol/kg of Mn(cyclam) caused the liver T1 relaxation rate to double at 15 minutes after injection. T1 measurements by pulsed MR imaging and manganese analyses on excised tissue showed that both relaxation rate (1/T1) and manganese content of liver and kidney increase linearly with the dosage of Mn(cyclam). The linear relationship between 1/T1 and manganese content can be considered an "in tissue" relaxivity plot for the agent. The resulting relaxivity is 54 mM-1sec-1 in liver, compared with 3.1 mM-1sec-1 in aqueous solution. Although this work is preliminary, the implication for medical MR imaging applications is that macrocyclic contrast agents can be effective at approximately one-tenth the current typical dose used for gadolinium DTPA.