Papers by Alexandre da Silveira
Birkhäuser advances in infectious diseases, 2019
The chronic phase of Chagas disease is presented in three clinical forms: indeterminate (no clini... more The chronic phase of Chagas disease is presented in three clinical forms: indeterminate (no clinical manifestations), cardiac disease, and megaviscera syndromes. The latter comprise up to 18% of the infected individuals and most often present a compromise of the esophagus and colon. The physiological function of these organs depends on a perfect coordination/synchronization of muscular constriction and relaxation waves, in order to push a rather hard material (alimentary bolus and feces) through their cavity, and a coordinated transposition of two sphincters. When this function is hampered, a progressive increase in the diameter of both organs is produced, termed megaesophagus and megacolon. A clue for the cause of this dysfunction is the selective destruction of parasympathetic plexus neurons by the etiological agent of the disease, Trypanosoma cruzi. Besides motor alterations, secretory and absorptive functions may be affected. Why these features are observed in only some of the infected is not clear. A markedly discrete geographical distribution of digestive Chagas disease cases below the equatorial line suggests it may be due to the type of circulating T. cruzi lineages (TcII and TcV). Different incidences according to gender and age are also seen. A number of neurotransmitters and neuropeptides have been linked to Chagas disease-associated megaviscera syndromes. Dysphagia and obstipation are clinical hallmarks of this disease, but serological diagnosis is necessary to exclude other possible causes, like idiopathic megaviscera. Association with cardiac involvement is observed in 20–30% of the cases, and 40% of the cases exhibit both megaesophagus and megacolon. Progression from mild to severe disease is seen in some of the cases, in which surgery is ultimately required. Fecaloma and volvulus are common complications of megacolon. In recent years, new methods have significantly improved post-surgery prognosis. Alternative treatments with botulinum toxin and by mechanical dilatation are indicated for specific cases. Other hollow viscera may be involved, albeit at lower frequencies, such as the stomach, duodenum, gallbladder, ureter, bladder, and others. However, these are usually also associated with megacolon and/or megaesophagus.
Parasitology Research, Feb 12, 2019
Chagas disease is caused by Trypanosoma cruzi and remains one of the most neglected diseases in L... more Chagas disease is caused by Trypanosoma cruzi and remains one of the most neglected diseases in Latin America. One of its clinical forms is Chagas megacolon. Despite being known for more than half a century, detailed causes are still obscure. Recent evidence indicates a close relationship between the immune system and the enteric nervous system in the etiology of chagasic megacolon pathology. It is believed that low expression of the 5-HT 3A serotonin receptor on lymphocytes could be linked to megacolon development. To test this hypothesis, this work investigated the distribution of CD4, CD8, and CD20 lymphocytes and their 5-HT 3A receptor expression. The results demonstrated that Chagas patients without megacolon present a higher expression of the 5-HT 3A receptor in all analyzed lymphocytes compared with Chagas patients with megacolon. These data suggest that the high expression of this receptor may lead to immunomodulation and prevent the development of Chagas megacolon.
Parasite Immunology, Mar 1, 2017
Chagas' disease is still reaching about 10 million people in the world. In South America, one of ... more Chagas' disease is still reaching about 10 million people in the world. In South America, one of the most severe forms of this disease is the megacolon, characterized by severe constipation, dilated sigmoid colon and rectum and severe malnutrition. Previous data suggested that mast cells and serotonin (5-hydroxytryptamine [5-HT]) expression How to cite this article: Freitas MAR, Segatto N, Tischler N, de Oliveira EC, Brehmer A, da Silveira ABM. Relation between mast cells concentration and serotonin expression in chagasic megacolon development. Parasite Immunology.
Colorectal Disease, Oct 1, 2013
Megacolon, chronic dilation of a colonic segment,is accompanied by extensive myenteric neuron los... more Megacolon, chronic dilation of a colonic segment,is accompanied by extensive myenteric neuron loss. However, this fails to explain unequivocally the formation of megacolon. We aimed to study further enteric structures that are directly or indirectly involved in colonic motility. From surgically removed megacolon segments of seven Chagasic patients, three sets of cryosections from oral, megacolonic and anal zones were immunohistochemically quadruple-stained for smooth-muscle actin (SMA), synaptophysin (SYN, for nerve fibres), S100 (glia) and c-Kit (interstitial cells of Cajal, ICCs). Values of area measurements were related to the appropriate muscle layer areas and these proportions were compared with those of seven non-Chagasic control patients. Whereas nerve and glia profile proportions did not mirror unequivocally the changes of Chagasic colon calibre (nondilation/dilation/nondilation), the proportions of SMA (i.e. muscle tissue density) and c-Kit (i.e. ICC density) did so: they decreased from the oral to the megacolonic segment but increased to the anal zones (muscle tissue density: control 68.3%, oral 54.3%, mega 42.1%, anal 47.6%; ICC-density: control 1.8%, oral 1.1%, mega 0.4, anal 0.8%). Of the parameters evaluated, muscle tissue and ICC densities may be involved in the formation of Chagasic megacolon, although the mechanism of destruction cannot be deduced.
2020 6th International Conference on Electric Power and Energy Conversion Systems (EPECS), 2020
The growing search for the electrical system modernization improve the development and implementa... more The growing search for the electrical system modernization improve the development and implementation of the microgrids concepts. Microgrids consists in a component of the distribution grid, with connected or isolated operation capabilities, and distributed energy resources within the electrical parameters' limits. Thus, this work presents an iterative optimization method to obtain the optimal sizing of a microgrid combined with a photovoltaic generation and a battery storage system. The objective of the optimization is to obtain the lowest value for the annual costs of the system (ACS), maximizing solar generation, subject to operational restrictions. After presenting the annual cost of the system, an average hourly price of the microgrid was calculated, resulting in 0,414 R$/kWh. This price is lower than average hourly price of utility tariffs. Hence, the results validated the proposed optimization method.
RAM. Revista de Administração Mackenzie, 2018
Purpose: The study presents a dynamic and complex procedural experience performed by small microb... more Purpose: The study presents a dynamic and complex procedural experience performed by small microbreweries in a cluster in Porto Alegre, Brazil. Thus, this article aims to establish theoretical propositions about coopetition strategies in this context. Originality/value: One of the gaps in the organizational studies is an understanding of how the process of developing a new strategic dynamic takes place. We consider coopetition to be a process that involves narrow strategies of simultaneous coopetition and cooperation between competing firms, in different areas and levels of interaction. Design/methodology/approach: Qualitative, exploratory research was conducted, using data triangulation and multiple methods. The case study technique was adopted to perform an in-depth examination of the phenomenon of secondary data collection, participant observations, and semi-structured interviews. Findings: The results showed that microbreweries are developing a strategic process of coopetition t...
Colorectal disease : the official journal of the Association of Coloproctology of Great Britain and Ireland, Jan 23, 2015
Chagas' disease is caused by the protozoan parasite Trypanosoma cruzi and during the past few... more Chagas' disease is caused by the protozoan parasite Trypanosoma cruzi and during the past few decades, it has become more frequent in cities in non-endemic countries, where it can be transmitted directly or by blood transfusion or organ transplantation. Clinical forms of the disease such as megacolon may occur several years after initial infection [1]. Recent reports indicate the development of megacolon may be associated with a disturbance of immune system and enteric nervous system (ENS). It is accepted that some agents such as serotonin, act on both systems and may provide a link between them [2]. This article is protected by copyright. All rights reserved.
Parasitology, 2008
SUMMARYChagas' disease is one of the few functional gastrointestinal disorders for which a ca... more SUMMARYChagas' disease is one of the few functional gastrointestinal disorders for which a causative agent has been identified. However, some pathological aspects of the chagasic megasyndromes are still incompletely understood. Chagasic megacolon is characterized by an inflammatory process, organ dilatation and neuronal reduction in both plexuses of the enteric nervous system (ENS). Although some studies on the ENS in Chagas' disease have been performed, the process of neuronal destruction and neuronal regeneration still remains unclear. Our hypothesis is that the regeneration process of the ENS may be involved with the mechanisms that prevent or retard organ dilatation and chagasic megacolon development. For that reason, we evaluated the neuronal regeneration with the marker GAP-43 in the colon's neuronal plexuses from chagasic patients with megacolon, and from non-infected individuals. Visual examination and quantitative analysis revealed an increased neuronal regenera...
Human Immunology, 2013
Chagas' disease is one of the most serious parasitic diseases of Latin America, with a social and... more Chagas' disease is one of the most serious parasitic diseases of Latin America, with a social and economic impact far outweighing the combined effects of other parasitic diseases such as malaria, leishmaniasis and schistosomiasis. In the chronic phase of this disease, the destruction of enteric nervous system (ENS) components leads to megacolon development. Previous data presented that the regeneration tax in the ENS neurons is augmented in chagasic patients. Although, there are several neuronal types with different functions in the intestine a detailed study about the regeneration of every neuronal type was never performed before. Therefore, the aim of this study was to evaluate the regeneration tax of every neuronal cell type in the ENS from chagasic patients with megacolon and non-infected individuals. A neuronal regeneration marker (GAP-43) was used in combination with a pan-neuronal marker (Peripherin) and several neuropeptides markers (cChat, Substance P, NPY, VIP and NOS), and it was considered as positive just with the combination of these markers. Our results demonstrated that the regeneration levels of cChat, Substance P, and NPY were similar in chagasic patients and non-infected individuals. However, levels of VIP and NOS neuropeptides were increased in chagasic patients when compared with noninfected individuals. We believe that the augment in the regeneration occur due to an increased destruction of selective neuronal types. These results corroborates with previous studies that pointed out to selective destruction of VIP and NOS neurons in chagasic patients.
Histochemistry and Cell Biology, 2011
The consequence of presence versus absence of mucosal neurons is not consistently assessed. Here,... more The consequence of presence versus absence of mucosal neurons is not consistently assessed. Here, we addressed two questions. First, based on resected gut specimens of 65 patients/body donors suffering from different diseases, counts of mucosal neurons per mm(2) were analysed with respect to age, gender and region. Second, we evaluated resected megacolonic specimens of four patients suffering from chronic Chagas' disease. Mucosal wholemounts were triple-stained for calretinin (CALR), peripherin (PER) and human neuronal protein Hu C/D (HU). Counts revealed no clear correlation between the presence of mucosal neurons and age, gender or region. Mucosal neurons were present in 30 of 36 specimens derived from males (83%) and in 20 of 29 from females (69%). The numbers per mm(2) increased from duodenum to ileum (1.7-10.8) and from ascending to sigmoid colon (3.2-9.9). Out of 149 small intestinal mucosal neurons, 47% were co-reactive for CALR, PER and HU (large intestine: 76% of 300 neurons) and 48% for PER and HU only (large intestine: 23%). In 12 megacolonic specimens (each 3 from 4 patients), all 23 mucosal neurons found (1.9 per mm(2)) displayed co-reactivity for CALR, PER and HU. We suggest that the presence or the absence of mucosal neurons is variable, ongoing studies will address our assumption that they correspond in their morphochemical characteristics to submucosal neurons. Furthermore, both the architecture and neuron number of the megacolonic mucosal plexus displayed no dramatic changes indicating that mucosal nerves might be less involved in chagasic/megacolonic neurodegeneration as known from the myenteric plexus.
Anorectal Physiology, 2020
Journal of Clinical Medicine, 2020
Mammalian organisms form intimate interfaces with commensal and pathogenic gut microorganisms. In... more Mammalian organisms form intimate interfaces with commensal and pathogenic gut microorganisms. Increasing evidence suggests a close interaction between gut microorganisms and the enteric nervous system (ENS), as the first interface to the central nervous system. Each microorganism can exert a different effect on the ENS, including phenotypical neuronal changes or the induction of chemical transmitters that interact with ENS neurons. Some pathogenic bacteria take advantage of the ENS to create a more suitable environment for their growth or to promote the effects of their toxins. In addition, some commensal bacteria can affect the central nervous system (CNS) by locally interacting with the ENS. From the current knowledge emerges an interesting field that may shape future concepts on the pathogen–host synergic interaction. The aim of this narrative review is to report the current findings regarding the inter-relationships between bacteria, viruses, and parasites and the ENS.
Aquatic Toxicology, 2020
For José Nuno Oliveira, on his 60th birthday A classical result in algebraic specification states... more For José Nuno Oliveira, on his 60th birthday A classical result in algebraic specification states that a total function defined on an initial algebra is a homomorphism if and only if the kernel of that function is a congruence. We expand on the discussion of that result from an earlier paper: extending it from total to partial functions, simplifying the proofs using relational calculus, and generalising the setting to regular categories.
Human pathology, 2008
The different concentrations of mast cells in the musculature of the esophagus and the colon ☆ We... more The different concentrations of mast cells in the musculature of the esophagus and the colon ☆ We studied Chagas disease in an endemic area in Brazil. This illness is caused by the protozoan parasite Trypanosoma cruzi, and the pathogenesis could involve fibrosis in the musculature of the esophagus and in the colon [1-3]. Previously, we related an increase of the mast cells counted in the colon musculature of chronic Chagas disease patients with megacolon, possibly indicating a relationship between mastocytosis and fibrosis [2,4]. Mast cells are involved in a wide variety of biological functions, and there is a direct cause-and-effect relationship between mast cell activation and the initiation of fibrosis and/or fibroblast activation and proliferation. Also, mast cells may participate directly in the fibrotic process through their ability to produce extracellular matrix glycoproteins. The aim of our study was to compare the concentration of mast cells in the muscular layer of the esophagus and the colon. Segments of the distal end of the esophagus and of the colon rectosigmoid transition were obtained from 12 patients submitted to necropsy. The patients had no diseases in the gastrointestinal tract, and the serology for the Chagas disease was negative for the 3 reactions. Morphometric study showed a significant difference (P b .0001) between the density of the mast cells in the circular musculature of the esophagus (9.12 mast cells/mm 2 , range, 1.42 to 29.6) and colon (0.08 mast cells/mm 2 , range, 0 to 1.9) in the same patients. Although these results were limited to mast cells in the circular muscular layer of the esophagus and colon, the differences between segments of the digestive tube could explain the differential behavior of the Chagas pathology between the esophagus and the colon. Also, other illnesses that are much more common in the esophagus than in other segments of the gastrointestinal tract could be clarified, such as scleroderma being systemic and the megaesophagus idiopathic [5].
Histochemistry and cell biology, Jan 29, 2017
Patients suffering from chagasic megacolon must have an intact mucosal barrier as they survive th... more Patients suffering from chagasic megacolon must have an intact mucosal barrier as they survive this chronic disease for decades. A key structure of the mucosal barrier are epithelial cells. Vasoactive-intestinal-peptide (VIP)-positive nerve fibres are involved in influencing, e.g., epithelial cell proliferation, mucus secretion (e.g., mucin 2 and trefoil factor 3 of goblet cells) and inflammation or autoimmunity, all putative and/or known factors altered in chagasic megacolon. We analyzed qualitatively and quantitatively goblet cells, their specific markers, such as mucin 2 (MUC2) and trefoil factor 3 (TFF3) and enterocytes, the relation of VIP-immunoreactive nerve fibres to the epithelia, the distribution of gelsolin, a protein involved in chronic inflammation processes in the epithelia, and the proliferation rate of epithelial cells by combined 4',6-diamidino-2-phenylindole (DAPI) and phosphohistone-H3 (PHH3) staining. Goblet cells were the dominating epithelial cell type. The...
International journal for parasitology, Jan 18, 2016
The aim of this work was to elucidate the immunopathological mechanisms of how helminths may infl... more The aim of this work was to elucidate the immunopathological mechanisms of how helminths may influence the course of a viral infection, using a murine model. Severe virulence, a relevant increase in the virus titres in the lung and a higher mortality rate were observed in Ascaris and Vaccinia virus (VACV) co-infected mice, compared with VACV mono-infected mice. Immunopathological analysis suggested that the ablation of CD8(+) T cells, the marked reduction of circulating CD4(+) T cells producing IFN-γ, and the robust pulmonary inflammation were associated with the increase of morbidity/mortality in co-infection and subsequently with the negative impact of concomitant pulmonary ascariasis and respiratory VACV infection for the host. On the other hand, when evaluating the impact of the co-infection on the parasitic burden, co-infected mice presented a marked decrease in the total number of migrating Ascaris lung-stage larvae in comparison with Ascaris mono-infection. Taken together, ou...
Histochemistry and Cell Biology, 2014
Springerlink.com neuron loss. Neurons co-immunoreactive for vIP and calretinin survived dispropor... more Springerlink.com neuron loss. Neurons co-immunoreactive for vIP and calretinin survived disproportionately. As a consequence, these neurons may have contributed to maintain the epithelial barrier and allowed the chagasic patients to survive for decades, despite their severe disturbance of colonic motility. Due to its neuroprotective and neuroeffectory functions, vIP may play a key role in the development and duration of chagasic megacolon. Keywords Chagas • enteric nervous system • Hirschsprung • Megacolon • vasoactive intestinal peptide Structural components of the human enteric nervous system The overwhelming majority of enteric neuronal cell bodies lie, together with enteric glial cells, in ganglionated nerve networks, the myenteric and the submucosal plexus. These differ in location and network architecture (Fig. 1) as well as in neuronal composition (see below). Situated between the longitudinal and the circular muscle layer is the myenteric plexus (Auerbach 1862). Its main, primary network is commonly monolayered and extends from the upper oesophageal to the internal anal sphincter. Most human myenteric neurons are either nitrergic or cholinergic (Murphy et al. 2007; Beck et al. 2009). Like in other species (best known from the guinea pig, Furness 2006), human nitrergic myenteric neurons are suggested to be either descending inter-and/or inhibitory motor neurons (Grider 1993). They are uniaxonal with spiny shaped dendrites (spiny type I morphology; Brehmer et al. 2004a; Lindig et al. 2009). Besides their reactivity for the nitrergic marker neuronal nitric oxide synthase (nNOS), some of them co-stain immunohistochemically for vasoactive Abstract Megacolon, the irreversible dilation of a colonic segment, is a structural sign associated with various gastrointestinal disorders. In its hereditary, secondary form (e.g. in Hirschsprung's disease), dilation occurs in an originally healthy colonic segment due to an anally located, aganglionic zone. In contrast, in chronic Chagas' disease, the dilated segment itself displays pathohistological changes, and the earliest and most prominent being found was massive loss of myenteric neurons. This neuron loss was partial and selective, i.e. some neurons containing neuronal nitric oxide synthase and/or vasoactive intestinal peptide (vIP) were spared from neuron death. This disproportionate survival of inhibitory neurons, however, did not completely correlate with the calibre change along the surgically removed, megacolonic segments. A better correlation was observed as to potentially contractile muscle tissue elements and the interstitial cells of Cajal. Therefore, the decreased densities of α-smooth muscle actin-and c-kitimmunoreactive profiles were estimated along resected megacolonic segments. Their lowest values were observed in the megacolonic zones itself, whereas less pronounced decreases were found in the non-dilated, transitional zones (oral and anal to dilation). In contrast to the myenteric plexus, the submucosal plexus displayed only a moderate
Cell and Tissue Research, 2014
Chagasic megacolon is accompanied by extensive myenteric and, simultaneously, moderate submucosal... more Chagasic megacolon is accompanied by extensive myenteric and, simultaneously, moderate submucosal neuron loss. Here, we examined changes of the innervation pattern of the lamina propria (LP) and muscularis mucosae (MM). Two alternating sets of cryosections were taken from seven nonchagasic colonic and seven chagasic megacolonic specimens (the latter included both the dilated megacolonic and the nondilated transitional oral and anal zones) and were immunohistochemically triple-stained for smooth-muscle actin (SMA), synaptophysin (SYN) and glial acid protein S100 and, alternatively, for SMA, vasoactive intestinal peptide (VIP) and somatostatin (SOM). Subsequent image analysis and statistical evaluation of nervous tissue profile areas revealed that, in LP, the most extreme differences (i.e. increase in thickness or decrease in nerve, glia and muscle tissue profile area, respectively) compared with control values occurred in the dilated megacolonic zone itself. In contrast, the most extreme differences in the MM were in the anal-tomegacolonic zone (except the profile area of muscle tissue, which was lowest in the megacolonic zone). This parallels our previous results in the external muscle coat. A partial and selective survival of VIP-immunoreactive in contrast to SOM-immunoreactive nerve fibres was observed in both mucosal layers investigated. Thus, VIPergic nerve elements might be crucial for the maintenance of the mucosal barrier. The differential changes of neural tissue parameters in LP and MM might reflect a multifactorial rather than a pure neurogenic development of megacolon in chronic Chagas' disease.
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Papers by Alexandre da Silveira