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Chagas' disease, caused by Trypanosoma cruzi, is an important cause of morbidity in many countries in Latin America. The important modes of transmission are by the bite of the reduviid bug and blood transfusion. The organism exists in three morphological forms: trypomastigotes, amastigotes, and epimastigotes. The mechanism of transformation and differentiation is currently being explored, and signal transduction pathways of the parasites may be involved in this process. Parasite adherence to and invasion of host cells is a complex process involving complement, phospholipase, penetrin, neuraminidase, and hemolysin. Two clinical forms of the disease are recognized, acute and chronic. During the acute stage pathological damage is related to the presence of the parasite, whereas in the chronic stage few parasites are found. In recent years the roles of tumor necrosis factor, gamma interferon, and the interleukins in the pathogenesis of this infection have been reported. The common manifestations of chronic cardiomyopathy are arrhythmias and thromboembolic events. Autoimmune, neurogenic, and microvascular factors may be important in the pathogenesis of the cardiomyopathy. The gastrointestinal tract is another important target, and "mega syndromes" are common manifestations. The diagnosis and treatment of this infection are active areas of investigation. New serological and molecular biological techniques have improved the diagnosis of chronic infection. Exacerbations of T. cruzi infection have been reported for patients receiving immuno-suppressive therapy and for those with AIDS.

Abstract. The recycling of synaptic vesicles in nerve terminals is thought to involve clathrin-coated vesicles. However, the properties of nerve terminal coated vesicles have not been characterized. Starting from a preparation of purified nerve terminals obtained from rat brain, we isolated clathrin-coated vesicles by a series of differential and density gradient centrifugation steps. The enrichment of coated vesicles during fractionation was monitored by EM. The final fraction consisted of >90 % of coated vesicles, with only negligible contamination by synaptic vesicles. Control experiments revealed that the contribution by coated vesicles derived from the axo-dendritic region or from nonneuronal cells is minimal.The membrane composition of nerve terminal-derived coated vesicles was very similar to that of synaptic vesicles, containing the membrane proteins synaptophysin, synaptotagmin, p29, synaptobrevin and the ll6-kD subunit of the vacuolar proton pump, in similar stoichiometric ratios. The small GTP-binding protein rab3A was absent, probably reflecting its dissociation from synaptic vesicles during endocytosis. Immunogold EM revealed that virtually all coated vesicles carried synaptic vesicle proteins, demonstrating that the contribution by coated vesicles derived from other membrane traffic pathways is negligible. Coated vesicles isolated from the whole brain exhibited a similar composition, most of them carrying synaptic vesicle proteins. This indicates that in nervous tissue, coated vesicles function predominantly in the synaptic vesicle pathway. Nerve terminal-derived coated vesicles contained AP-2 adaptor complexes, which is in agreement with their plasmalemmal origin. Furthermore, the neuron-specific coat proteins AP 180 and auxilin, as well as the eta1-and act-adaptins, were enriched in this fraction, suggesting a function for these coat proteins in synaptic vesicle recycling.

). There are currently eight known subtypes of mGlu receptors, which are divided into three groups based on sequence homology, pharmacology and signal transduction mechanisms. There is evidence that mGlu receptors have a role in the induction of various forms of synaptic plasticity such as long-term potentiation and long-term depression (LTD) (Anwyl, 1999;Bortolotto et al. 1999).Synaptic activation of mGlu receptors has been shown to be involved in LTD induction under a variety of experimental conditions (Stanton et al. 1991; Bashir et al. 1993;Bolshakov & Siegelbaum, 1994;Oliet et al. 1997;Fitzjohn et al. 1998a;Kemp & Bashir, 1999;Huber et al. 2000). However, mGlu receptor-dependent LTD often coexists at the same synapses with NMDA receptordependent LTD (e.g. Oliet et al. 1997). One strategy to selectively activate mGlu receptor-dependent LTD is to apply a specific mGlu receptor agonist. The broad spectrum mGlu receptor agonist 1-aminocyclopentane-1,3-dicarboxylic acid (ACPD) has been shown to induce LTD in both the dentate gyrus (O'Mara et al. 1995) 1. In the CA1 region of hippocampal slices prepared from juvenile (12-to 18-day-old) rats, activation of group I metabotropic L-glutamate (mGlu) receptors by the specific agonist (RS)-3,5-dihydroxyphenylglycine (DHPG) induces a form of long-term depression (LTD) of excitatory synaptic transmission.2. We have used a variety of electrophysiological techniques applied to CA1 neurones in hippocampal slices and from pyramidal cells in dissociated hippocampal cultures to investigate the Ca 2+ dependence and locus of expression of DHPG-induced LTD.3. In patch-clamp experiments from hippocampal slices, bath application of DHPG induced a depression of synaptically evoked responses that persisted for the duration of the recording (up to 2 h after commencing washout of DHPG) in 27 of 29 neurones investigated.4. DHPG-induced LTD was associated with an increase in both the paired-pulse facilitation ratio and the coefficient of variation of EPSCs.5. Using dendritic recording, there was a decrease in EPSC success rate (number of trials that elicited a detectable response) but no change in potency (mean EPSC amplitude excluding failures) associated with DHPG-induced LTD.6. In experiments using dissociated hippocampal cultures, application of DHPG elicited a persistent decrease in the frequency of tetrodotoxin-resistant miniature EPSCs but no change in the amplitude of such events.7. DHPG-induced LTD was not blocked by intracellular application of the calcium chelator BAPTA. It was also unaffected when intracellular calcium stores were depleted by perfusion with thapsigargin. Furthermore, when synaptic transmission was blocked by perfusing with Ca 2+ -free medium, DHPG application reliably induced LTD.8. These data suggest that DHPG-induced LTD is Ca 2+ independent and is expressed presynaptically.

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