Endoscopic and surgical treatment of non-neoplastic proximal duodenal ulceration in dogs, and anatomical study of proximal duodenal vascularisation.

OBJECTIVES: Proximal duodenal ulceration is often characterised by continuous bleeding, and treatment is challenging. The aims of this study were to investigate the role of vascularisation in proximal duodenal ulceration and describe clinical aspects, endoscopic features and treatment in dogs. MATERIAL AND METHODS: Polyurethane foam casts of gastroduodenal vessels were obtained from five dogs which had died from disorders unrelated to the digestive system. In addition, 12 dogs having proximal duodenal ulcers diagnosed by endoscopic examination were enrolled in a treatment trial. After the endoscopic diagnosis of a duodenal ulcer, all the dogs were treated medically and, in the absence of resolution, were subsequently treated by endoscopic electrocauterisation or by surgery. RESULTS: A submucosal vascular network was evident in all the casts, with a prominent venous plexus seen exclusively in the first half inch of the duodenum. In clinical cases, on endoscopic examination, the duodenal ulcer was located at the proximal part of the duodenum, involving the mesenteric portion of the wall. The dogs not responding to medical treatment (6/12) were treated with endoscopic electrocauterisation, surgical coagulation or resection of the proximal duodenal portion. All the dogs survived until discharge, and the median survival time following discharge was 107.5 days. CLINICAL SIGNIFICANCE: Based on the anatomical details highlighted in this study, the continuous bleeding observed in our patients may have been due to the prominent venous plexus evidenced at the level of the proximal duodenum. Surgical and endoscopic treatments in six patients resolved the ulcer bleeding with no recurrences noted during follow-up.

Muscarinic modulation of neurotransmission: the effects of some agonists and antagonists.

1. Functional studies were performed to evaluate the effects of some muscarinic agents at the neuromuscular junction of the mouse. 2. The presynaptic control of acetylcholine release and the postsynaptic activation of the nicotinic receptor have been analyzed by means of extracellular recording. The amplitude of spontaneous and of evoked acetylcholine release, the frequency of spontaneous acetylcholine release and the time course of the quantal release have been measured by means of an EPC7 patch clamp amplifier. 3. This electrophysiological method revealed multiple dose-related effects of some agonists and antagonists on the above parameters. Concentration-response curves related to the parameters underlying the function of this cholinergic synapse were obtained and the apparent EC50 values calculated. 4. Many of the interactions of the agonists and antagonists could inhibit neuromuscular transmission. The rank order potencies related to the inhibition of the evoked signals were carbachol > oxotremorine > d,l-muscarine for the agonists and methoctramine > 4-DAMP > l-hyoscyamine > AFDX-116 > ipratropium > pirenzepine for the antagonists. 5. These findings suggest a more complicated pattern related to the muscarinic action at the mouse neuromuscular junction with the involvement of some post-synaptic located sites.

Postsynaptic effects of methoctramine at the mouse neuromuscular junction.

Functional studies were performed to evaluate the effects of methoctramine at the neuromuscular junction of the mouse. The presynaptic control of acetylcholine release and the postsynaptic activation of the nicotinic receptor have been analysed by means of the extracellular recording with an EPC7 Patch Clamp amplifier. This electrophysiological method revealed a dose-related inhibitory effect of methoctramine on the studied parameters. The dramatic reduction of the kinetics of the quantal conductance change indicates an action at the postsynaptic level. The effects of methoctramine have been compared with those of the muscarinic agonist oxotremorine. Concentration/response curves for the two drugs were obtained and the apparent EC50 values calculated. The effects of oxotremorine were not antagonized by 1 microM methoctramine. These findings suggest an interaction of some muscarinic agents on the postsynaptic receptor-ion-channel complex at the mouse neuromuscular junction.

[Presynaptic effects induced by pretreatment with formamide of the neuromuscular junction of the mouse]. / Effetti presinaptici indotti dal pretrattamento con formamide sulla guinzione neuromuscolare di topo.

Some techniques to block muscular nerve evoked contraction involve pharmacological approaches using synaptic blocking agents. Such methods interfere with normal synaptic transmission, and could introduce artifacts making difficult the experimental interpretation. The method based on the use of formamide pre-treatment should not interfere with synaptic physiology, indeed previous works suggest that the mechanism involved in block of muscle activity could depend on the decrease in specific postsynaptic membrane capacitance, and on the disruption of the morphology of the transverse tubule system. To prove this assumption we evaluated before and after formamide pre-treatment, some pre and postsynaptic parameters related to the spontaneous quantal release (MEPC). By means of the Loose patch clamp technique, we demonstrated, that formamide pre-treatment increases in an irreversible manner the frequency of spontaneous quantal release. Morphology of MEPC appear not modified by formamide pretreatment, which does not interfere with postsynaptic cholinergic receptors activity.