ABSTRACT
Background/Aims@#Chagasic megacolon is caused by Trypanosoma cruzi, which promotes in several cases, irreversible segmental colonic dilation. This alteration is the major anatomic-clinical disorder, characterized by the enteric nervous system and muscle wall structural damage. Herein, we investigate how T. cruzi-induced progressive colonic structural changes modulate the colonic contractile pattern activity. @*Methods@#We developed a murine model of T. cruzi-infection that reproduced long-term modifications of the enlarged colon. We evaluated colonic and total intestinal transit time in animals. The patterns of motor response at several time intervals between the acute and chronic phases were evaluated using the organ bath assays. Enteric motor neurons were stimulated by electric field stimulation. The responses were analyzed in the presence of the nicotinic and muscarinic acetylcholine receptor antagonists. Western blot was performed to evaluate the expression of nicotinic and muscarinic receptors. The neurotransmitter expression was analyzed by real-time polymerase chain reaction. @*Results@#In the chronic phase of infection, there was decreased intestinal motility associated with decreased amplitude and rhythmicity of intestinal contractility. Pharmacological tests suggested a defective response mediated by acetylcholine receptors. The contractile response induced by acetylcholine was decreased by atropine in the acute phase while the lack of its action in the chronic phase was associated with tissue damage, and decreased expression of choline acetyltransferase, nicotinic subunits of acetylcholine receptors, and neurotransmitters. @*Conclusions@#T. cruzi-induced damage of smooth muscles was accompanied by motility disorders such as decreased intestinal peristalsis and cholinergic system response impairment. This study allows integration of the natural history of Chagasic megacolon motility disorders and opens new perspectives for the design of effective therapeutic.
ABSTRACT
This study reports the concentrations of important tracers of the marine environment, [210]Po and [210]Pb, in different matrices from field samples collected at Central Adriatic Sea [Italy], a non-contaminated marine ecosystem. [210]Po concentration appears to decrease with increasing distance from the coast and a significant difference in [210]Po concentrations in seawater samples at two different depths is not appreciable. [210]Po and [210]Pb present the same trend in the different periods of the year. [210]Po and [210]Pb present high concentration factors and high Kd values: in particular [210]Po shows values of 2.4 10[4] in plankton, 3.2 10[5] in the particulate fraction and 1.1 10[5] in sediment; [210]Pb shows values of 1.3 10[4] in plankton, 1.8 10[4] in the particulate fraction and 4.9 10[4] in sediment. The [210]Po/[210]Pb ratio results < 1 in sea water and >1 in the particulate fraction, sediment and plankton due to a significant fractionation occurring between the two radionuclides during their removal from solution to particle and due to their different biogeochemical cycling pathways in the marine environment. The noticeable accumulation of [210]Po in the food chain is not accompanied by an identical accumulation of [210]Pb. Due to its biomagnification in the marine food chain, [210]Po provides the larges radiation dose to any marine organism under natural conditions. The data reported provide reference values for the Central Adriatic [Mediterranean Sea] coastal environment