Angiotensinase activity is asymmetrically distributed in the amygdala, hippocampus and prefrontal cortex of the rat.

There are important asymmetries in brain functions such as emotional processing and stress response in humans and animals. Knowledge of the bilateral distribution of brain neurotransmitters is important to appropriately understand its functions. Some peptides such as those included in the renin-angiotensin system (RAS) and cholecystokinin (CCK) are related to modulation of behavior and stress. However, although angiotensin AT1 and CCK type 2 receptors were found in adult rat brain, there are no studies of their bilateral distribution in stress-related areas. The function of angiotensin peptides is depending on the action of several aminopeptidases (AP) called angiotensinases, some of them being also involved in the metabolism of CCK. We have studied the bilateral distribution of soluble (SOL) and membrane-bound (MEM) alanyl- (AlaAP), cystinyl- (CysAP), glutamyl- (GluAP) and aspartyl- (AspAP) AP activities in stress-related areas such as amygdala, hippocampus and medial prefrontal cortex of adult male rats in resting conditions. These enzymes are involved in the metabolism of angiotensins (AlaAP, CysAP, GluAP, AspAP) and CCK (GluAP, AspAP). In the amygdala, all the activities studied showed a right predominance with a significant difference ranging from 30% for SOL CysAP to 125% for SOL GluAP. In the hippocampus, there was a left predominance for SOL AlaAP, SOL and MEM CysAP and MEM AspAP activities (100, 80, 300 and 100% higher, respectively). In contrast, GluAP predominated remarkably in the right hippocampus (eight-fold for SOL and three-fold for MEM). In the prefrontal cortex, SOL and MEM CysAP and SOL AspAP predominated in the left hemisphere (40, 100 and 40% higher, respectively). These results demonstrated a heterogeneous bilateral pattern of angiotensinase activities in motivation and stress-related areas. This may reflect an uneven asymmetrical distribution of their endogenous substrates depending on the brain location and consequently, it would be also a reflect of the asymmetries in the functions they are involved in.

SNARE protein-dependent glutamate release from astrocytes.

We investigated the cellular mechanisms underlying the Ca(2+)-dependent release of glutamate from cultured astrocytes isolated from rat hippocampus. Using Ca(2+) imaging and electrophysiological techniques, we analyzed the effects of disrupting astrocytic vesicle proteins on the ability of astrocytes to release glutamate and to cause neuronal electrophysiological responses, i.e., a slow inward current (SIC) and/or an increase in the frequency of miniature synaptic currents. We found that the Ca(2+)-dependent glutamate release from astrocytes is not caused by the reverse operation of glutamate transporters, because the astrocyte-induced glutamate-mediated responses in neurons were affected neither by inhibitors of glutamate transporters (beta-threo-hydroxyaspartate, dihydrokainate, and L-trans-pyrrolidine-2,4-dicarboxylate) nor by replacement of extracellular sodium with lithium. We show that Ca(2+)-dependent glutamate release from astrocytes requires an electrochemical gradient necessary for glutamate uptake in vesicles, because bafilomycin A(1), a vacuolar-type H(+)-ATPase inhibitor, reduced glutamate release from astrocytes. Injection of astrocytes with the light chain of the neurotoxin Botulinum B that selectively cleaves the vesicle-associated SNARE protein synaptobrevin inhibited the astrocyte-induced glutamate response in neurons. Therefore, the Ca(2+)-dependent glutamate release from astrocytes is a SNARE protein-dependent process that requires the presence of functional vesicle-associated proteins, suggesting that astrocytes store glutamate in vesicles and that it is released through an exocytotic pathway.

Idiopathic dialysis ascites in the nineties: resolution after renal transplantation.

The incidence of idiopathic dialysis ascites seems to have decreased since the introduction of more effective techniques for control of fluid overload and uremia in chronic hemodialysis patients. Most of the patients reported so far had some predisposing factor, such as malnutrition or sustained fluid overload. We report a case of idiopathic dialysis ascites in a young well-nourished woman with an excellent control of fluid overload and in whom biocompatible dialyzer membranes and volumetric controlled ultrafiltration had been used since her onset of chronic dialysis. Extensive studies excluded the existence of an underlying cause for ascites. Ascitic fluid had the characteristics of an exudate, and a peritoneal biopsy specimen showed chronic nonspecific inflammatory changes. Massive ascites persisted for 6 months, requiring repeated paracentesis, until the performance of a successful renal transplantation. Coinciding with the recovery of renal function, a dramatic disappearance of ascites was observed.

Evolution of immunoglobulin A nephropathy into Henoch-Schönlein purpura in an adult patient.

We report the first case of the evolution of immunoglobulin A (IgA) nephropathy into Henoch-Schönlein purpura in an adult patient. A 28-year-old man presented with an episode of gross hematuria and acute renal failure. The serum IgA level was increased and renal biopsy findings were diagnostic of IgA nephropathy. In addition, many renal tubuli were filled by red blood cell casts and presented a marked tubular necrosis. Coincidental with the disappearance of gross hematuria, renal function progressively improved. The patient continued to have microhematuria, normal renal function, and isolated bouts of macroscopic hematuria. Ten years later, the patient developed arthralgias, a purpuric rash in the legs, gross hematuria, and an elevated serum creatinine level. A skin biopsy showed leukocytoclastic vasculitis with IgA deposits. The renal biopsy showed histologic lesions very similar to those observed in the first biopsy 10 years before: mesangial proliferation with mesangial deposition of IgA and tubular necrosis with obstruction of renal tubuli by red blood cell casts. The serum creatinine level returned to normal. Recurrent episodes of purpura associated with macroscopic hematuria persisted during the follow-up, but without worsening of renal function. An interesting feature of our patient was the development of reversible renal failure associated with macroscopic hematuria on two different occasions. Although this complication has been described in IgA nephropathy, it has been rarely reported in Henoch-Schönlein purpura. It is possible that IgA nephropathy and Henoch-Schönlein purpura are different clinical manifestations of the same disease and probably share a common pathogenesis. Our case is a demonstrative example of this hypothesis.

Compressive myelopathy due to dialysis-associated amyloidosis.

A 66-year-old woman presented a spastic quadriparesis due to compression of the cervical cord 6 years after the beginning of chronic hemodialysis. Five years later, she developed a second episode of compressive myelopathy affecting the lumbar spine. On both occasions, surgical laminectomy with removal of fibroligamentous rings that compressed the cord led to a total recovery of the patient. Histological study demonstrated the presence of massive amyloid deposits in the surgically excised material.