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Sample records for experimental acute chagas

  1. Experimental Chagas' disease in dogs

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    Marta de Lana

    1992-03-01

    Full Text Available This paper describes the development of experimental Chagas' disease in 64 out-bred young dogs. Twenty-nine animals were inoculated with the Be-62 and 35 with Be-78 Trypanosoma cruzi strains. Twenty-six were infected with blood trypomastigotes by different inoculation routes and 38 with metacyclic trypomastigotes from the vector via the conjunctival route. Twenty of the 26 dogs infected with blood trypomastigotes were autopsied during the acute phase. Eleven died spontaneously and nine were sacrificed. Six remained alive until they died suddenly (two or were autopsied (four. Twelve of the 38 dogs infected with metacyclic trypomastigotes evolved naturally to the chronic phase and remained alive for 24-48 months. The parasitemia, clinical aspects and serology (IgM and IgG as well as electrocardiogram, hemogram and heart anatomo-histopathologic patterns of acute and chronic cardiac forms of Chagas' disease as seen in human infections, were reproduced. The most important finding is the reproductibility of diffuse fibrosing chronic chagasic cardiopathy in all dogs infected with Be-78 T. cruzi strain autopsied between the 90th and 864th days of infection. Thus, the dog can be considered as a suitable experimental model to study Chagas' disease according to the requisites of the World Health Organization (1984. Futhermore the animal is easily obtained and easy to handle and maintain in experimental laboratory conditions.

  2. Alterações quantitativas das células de purkinje na moléstia de chagas experimental no camundongo Quantitative study of Purkinje cells in the acute phase of experimental Chagas' disease

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    Edymar Jardim

    1967-09-01

    Full Text Available O autor estudou quantitativamente as células de Purkinje em cortes semi-seriados do cerebelo de camundongos inoculados experimentalmente com T. cruzi,tendo verificado considerável destruição neuronal na fase aguda da enfermidade.A quantitative study of Purkinje cells was done through semi-serial sections of cerebellum of mice experimentally innoculated by Trypanosoma cruzi. Avery marked neuronal destruction was found in the acute phase of Chagas' disease.

  3. Elucidating the impact of low doses of nano-formulated benznidazole in acute experimental Chagas disease.

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    Marcela S Rial

    2017-12-01

    Full Text Available Chagas disease is a neglected parasitic infection caused by the protozoan Trypanosoma cruzi (T. cruzi that affects more than 6 million people, mainly in Latin America. Benznidazole is still the drug of choice in many countries to treat it in spite of its dosage regimen and adverse side effects such as such as allergic dermatitis, peripheral neuropathy and anorexia. Thus, novel, safer, and more efficacious treatments for such neglected infection are urgently required.In this study, the efficacy of orally administered low doses of benznidazole (BNZ nanoparticles was evaluated during the acute phase in mice infected with T. cruzi Nicaragua (TcN that were immunosuppressed during the chronic stage of the disease. Moreover, the production of T. cruzi-specific antibodies, cardiac tissue inflammation and reactive oxygen species generation by Vero cells treated with both BNZ nanoparticles (BNZ-nps and raw BNZ (R-BNZ were also evaluated.T. cruzi infected mice treated with 10, 25 or 50 mg/kg/day of BNZ-nps survived until euthanasia (92 days post infection (dpi, while only 15% of infected untreated mice survived until the end of the experiment. PCR analysis of blood samples taken after induction of immunosuppression showed that a dosage of 25 mg/kg/day rendered 40% of the mice PCR-negative. The histological analysis of heart tissue showed a significant decrease in inflammation after treatments with 25 and 50 mg/kg/day, while a similar inflammatory damage was observed in both infected mice treated with R-BNZ (50 mg/kg/day and untreated mice. In addition, only BNZ-nps treated mice led to lower levels of T. cruzi-specific antibodies to 50-100%. Finally, mammalian Vero cells treated with BNZ-nps or R-BNZ lead to a significant increase in ROS production.Based on these findings, this research highlights the in-vitro/in-vivo efficacy of nanoformulated BNZ against T. cruzi acute infections in immunosuppressed and non-immunosuppressed mice and provides further

  4. Proteins involved on TGF-β pathway are up-regulated during the acute phase of experimental Chagas disease.

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    Ferreira, Roberto Rodrigues; de Souza, Elen Mello; de Oliveira, Fabiane Loiola; Ferrão, Patrícia Mello; Gomes, Leonardo Henrique Ferreira; Mendonça-Lima, Leila; Meuser-Batista, Marcelo; Bailly, Sabine; Feige, Jean Jacques; de Araujo-Jorge, Tania Cremonini; Waghabi, Mariana Caldas

    2016-05-01

    Studies developed by our group in the last years have shown the involvement of TGF-β in acute and chronic Chagas heart disease, with elevated plasma levels and activated TGF-β cell signaling pathway as remarkable features of patients in the advanced stages of this disease, when high levels of cardiac fibrosis is present. Imbalance in synthesis and degradation of extracellular matrix components is the basis of pathological fibrosis and TGF-β is considered as one of the key regulators of this process. In the present study, we investigated the activity of the TGF-β signaling pathway, including receptors and signaling proteins activation in the heart of animals experimentally infected with Trypanosoma cruzi during the period that mimics the acute phase of Chagas disease. We observed that T. cruzi-infected animals presented increased expression of TGF-β receptors. Overexpression of receptors was followed by an increased phosphorylation of Smad2/3, p38 and ERK. Furthermore, we correlated these activities with cellular factors involved in the fibrotic process induced by TGF-β. We observed that the expression of collagen I, fibronectin and CTGF were increased in the heart of infected animals on day 15 post-infection. Correlated with the increased TGF-β activity in the heart, we found that serum levels of total TGF-β were significantly higher during acute infection. Taken together, our data suggest that the commitment of the heart associates with increased activity of TGF-β pathway and expression of its main components. Our results, confirm the importance of this cytokine in the development and maintenance of cardiac damage caused by T. cruzi infection. Copyright © 2016 Elsevier GmbH. All rights reserved.

  5. Pathology of intracardiac nerves in experimental Chagas disease

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    Ribeiro Lídia Cristina Villela

    2002-01-01

    Full Text Available Severe destruction of intrinsic cardiac nerves has been reported in experimental acute Chagas myocarditis, followed by extensive regeneration during the chronic phase of the infection. To further study this subject, the sympathetic and para-sympathetic intracardiac nerves of mice infected with a virulent Trypanosoma cruzi strain were analyzed, during acute and chronic infection, by means of histological, histochemical, morphometric and electron microscopic techniques. No evidences of destructive changes were apparent. Histochemical demonstration for acetylcholinesterase and catecholamines did not reveal differences in the amount and distribution of intracardiac nerves, in mice with acute and chronic Chagas myocarditis or in non-infected controls. Mild, probably reversible ultrastructural neural changes were occasionally present, especially during acute myocarditis. Intrinsic nerves appeared as the least involved cardiac structure during the course of experimental Chagas disease in mice.

  6. Curcumin Enhances the Anti-Trypanosoma cruzi Activity of Benznidazole-Based Chemotherapy in Acute Experimental Chagas Disease.

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    Novaes, Rômulo Dias; Sartini, Marcus Vinicius Pessoa; Rodrigues, João Paulo Ferreira; Gonçalves, Reggiani Vilela; Santos, Eliziária Cardoso; Souza, Raquel Lopes Martins; Caldas, Ivo Santana

    2016-06-01

    Although curcumin can increase the effectiveness of drugs against malaria, combination therapies using the molecule have never been investigated in Chagas disease (ChD). Therefore, we evaluated the efficacy of curcumin as a complementary strategy to benznidazole (Bz)-based chemotherapy in mice acutely infected with Trypanosoma cruzi Eighty-four 12-week-old Swiss mice were equally randomized into seven groups: uninfected (NI), T. cruzi infected and untreated (INF), infected and treated with 100 mg/kg of body weight Bz (B100), 50 mg/kg Bz (B50), 100 mg/kg curcumin (C100), 100 mg/kg Bz plus 100 mg/kg curcumin (B100 plus C100), and 50 mg/kg Bz plus 100 mg/kg curcumin (B50 plus C100). After microscopic identification of blood trypomastigotes (4 days after inoculation), both drugs were administered by gavage once a day for 20 days. Curcumin showed limited antiparasitic, anti-inflammatory, and antioxidant effects when administered alone. When curcumin and Bz were combined, there was a drastic reduction in parasitemia, parasite load, mortality, anti-T. cruzi IgG reactivity, circulating levels of cytokines (gamma interferon [IFN-γ], interleukin 4 [IL-4], and MIP1-α), myocardial inflammation, and morphological and oxidative cardiac injury; these results exceeded the isolated effects of Bz. The combination of Bz and curcumin was also effective at mitigating liver toxicity triggered by Bz, increasing the parasitological cure rate, and preventing infection recrudescence in noncured animals, even when the animals were treated with 50% of the recommended therapeutic dose of Bz. By limiting the toxic effects of Bz and enhancing its antiparasitic efficiency, the combination of the drug with curcumin may be a relevant therapeutic strategy that is possibly better tolerated in ChD treatment than Bz-based monotherapy. Copyright © 2016, American Society for Microbiology. All Rights Reserved.

  7. Eosinophil levels in the acute phase of experimental chagas' disease Níveis de eosinófilos na fase aguda da doença de Chagas experimental

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    Maria Cristina Nakhle

    1989-12-01

    Full Text Available Eosinophil dynamics, in bone marrow, blood and peritoneal exudate, of resistant C57B1/6 (C57 and susceptible A/Snell (A/Sn mice was comparatively studied during the acute phase of infection by Trypanosoma cruzi Y strain. A decline was observed in bone marrow eosinophil levels in A/Sn, but not in C57 mice, soon after infection, those of the former remaining significantly below those of the latter up to the 4th day of infection. Bone marrow eosinophil levels of C57 mice declined subsequently to levels comparable to those of A/Sn mice, the number of these cells in this compartment remaining 50% those of non infected controls, in both strains, up to the end of the experiment on the 14th day of infection. The fluctuations in eosinophil levels in blood and peritoneal space were similar in both mice strains studied. Concomitantly with depletion of eosinophils in the marrow, depletion in blood and a marked rise of these cells in the peritoneal space, initial site of infection, occurred in both strains. The difference in eosinophil bone marrow levels, between C57 and A/Sn mice, observed in the first four days of infection, suggests a higher eosinopoiesis capacity of the former in this period, which might contribute to their higher resistance to T. cruzi infection.A dinâmica de eosinófilos, na medula óssea, sangue e exsudato peritoneal, de uma linhagem de camundongos resistente (C57B1/6 e de uma susceptível (A/Snell foi comparativamente estudada durante a fase aguda da infecção com a cepa Y do Trypanosoma cruzi. Foi observada uma queda nos níveis de eosinófilos da medula óssea nos camundongos A/Sn, mas não nos C57, logo após a infecção, os dos primeiros permanecendo significativamente abaixo dos níveis dos últimos até o 4? dia de infecção. Os níveis de eosinófilos da medula óssea nos camundongos C57 caíram subseqüentemente a níveis próximos aos dos camundongos A/Sn, o número destas células neste compartimento permanecendo em

  8. Experimental Vaccines against Chagas Disease: A Journey through History

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    Olivia Rodríguez-Morales

    2015-01-01

    Full Text Available Chagas disease, or American trypanosomiasis, which is caused by the protozoan parasite Trypanosoma cruzi, is primarily a vector disease endemic in 21 Latin American countries, including Mexico. Although many vector control programs have been implemented, T. cruzi has not been eradicated. The development of an anti-T. cruzi vaccine for prophylactic and therapeutic purposes may significantly contribute to the transmission control of Chagas disease. Immune protection against experimental infection with T. cruzi has been studied since the second decade of the last century, and many types of immunogens have been used subsequently, such as killed or attenuated parasites and new DNA vaccines. This primary prevention strategy appears feasible, effective, safe, and inexpensive, although problems remain. The objective of this review is to summarize the research efforts about the development of vaccines against Chagas disease worldwide. A thorough literature review was conducted by searching PubMed with the terms “Chagas disease” and “American trypanosomiasis” together with “vaccines” or “immunization”. In addition, reports and journals not cited in PubMed were identified. Publications in English, Spanish, and Portuguese were reviewed.

  9. Experimental Vaccines against Chagas Disease: A Journey through History.

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    Rodríguez-Morales, Olivia; Monteón-Padilla, Víctor; Carrillo-Sánchez, Silvia C; Rios-Castro, Martha; Martínez-Cruz, Mariana; Carabarin-Lima, Alejandro; Arce-Fonseca, Minerva

    2015-01-01

    Chagas disease, or American trypanosomiasis, which is caused by the protozoan parasite Trypanosoma cruzi, is primarily a vector disease endemic in 21 Latin American countries, including Mexico. Although many vector control programs have been implemented, T. cruzi has not been eradicated. The development of an anti-T. cruzi vaccine for prophylactic and therapeutic purposes may significantly contribute to the transmission control of Chagas disease. Immune protection against experimental infection with T. cruzi has been studied since the second decade of the last century, and many types of immunogens have been used subsequently, such as killed or attenuated parasites and new DNA vaccines. This primary prevention strategy appears feasible, effective, safe, and inexpensive, although problems remain. The objective of this review is to summarize the research efforts about the development of vaccines against Chagas disease worldwide. A thorough literature review was conducted by searching PubMed with the terms "Chagas disease" and "American trypanosomiasis" together with "vaccines" or "immunization". In addition, reports and journals not cited in PubMed were identified. Publications in English, Spanish, and Portuguese were reviewed.

  10. Behavioural alterations are independent of sickness behaviour in chronic experimental Chagas disease

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    Glaucia Vilar-Pereira

    2015-12-01

    Full Text Available The existence of the nervous form of Chagas disease is a matter of discussion since Carlos Chagas described neurological disorders, learning and behavioural alterations in Trypanosoma cruzi-infected individuals. In most patients, the clinical manifestations of the acute phase, including neurological abnormalities, resolve spontaneously without apparent consequence in the chronic phase of infection. However, chronic Chagas disease patients have behavioural changes such as psychomotor alterations, attention and memory deficits, and depression. In the present study, we tested whether or not behavioural alterations are reproducible in experimental models. We show that C57BL/6 mice chronically infected with the Colombian strain of T. cruzi (150 days post-infection exhibit behavioural changes as (i depression in the tail suspension and forced swim tests, (ii anxiety analysed by elevated plus maze and open field test sand and (iii motor coordination in the rotarod test. These alterations are neither associated with neuromuscular disorders assessed by the grip strength test nor with sickness behaviour analysed by temperature variation sand weight loss. Therefore, chronically T. cruzi-infected mice replicate behavioural alterations (depression and anxiety detected in Chagas disease patients opening an opportunity to study the interconnection and the physiopathology of these two biological processes in an infectious scenario.

  11. In vitro and in vivo experimental models for drug screening and development for Chagas disease

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    Alvaro José Romanha

    2010-03-01

    Full Text Available Chagas disease, a neglected illness, affects nearly 12-14 million people in endemic areas of Latin America. Although the occurrence of acute cases sharply has declined due to Southern Cone Initiative efforts to control vector transmission, there still remain serious challenges, including the maintenance of sustainable public policies for Chagas disease control and the urgent need for better drugs to treat chagasic patients. Since the introduction of benznidazole and nifurtimox approximately 40 years ago, many natural and synthetic compounds have been assayed against Trypanosoma cruzi, yet only a few compounds have advanced to clinical trials. This reflects, at least in part, the lack of consensus regarding appropriate in vitro and in vivo screening protocols as well as the lack of biomarkers for treating parasitaemia. The development of more effective drugs requires (i the identification and validation of parasite targets, (ii compounds to be screened against the targets or the whole parasite and (iii a panel of minimum standardised procedures to advance leading compounds to clinical trials. This third aim was the topic of the workshop entitled Experimental Models in Drug Screening and Development for Chagas Disease, held in Rio de Janeiro, Brazil, on the 25th and 26th of November 2008 by the Fiocruz Program for Research and Technological Development on Chagas Disease and Drugs for Neglected Diseases Initiative. During the meeting, the minimum steps, requirements and decision gates for the determination of the efficacy of novel drugs for T. cruzi control were evaluated by interdisciplinary experts and an in vitro and in vivo flowchart was designed to serve as a general and standardised protocol for screening potential drugs for the treatment of Chagas disease.

  12. Acute Chagas Disease: New Global Challenges for an Old Neglected Disease

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    Andrade, Daniela V.; Gollob, Kenneth J.; Dutra, Walderez O.

    2014-01-01

    Chagas disease is caused by infection with the protozoan Trypanosoma cruzi, and although over 100 years have passed since the discovery of Chagas disease, it still presents an increasing problem for global public health. A plethora of information concerning the chronic phase of human Chagas disease, particularly the severe cardiac form, is available in the literature. However, information concerning events during the acute phase of the disease is scarce. In this review, we will discuss (1) the current status of acute Chagas disease cases globally, (2) the immunological findings related to the acute phase and their possible influence in disease outcome, and (3) reactivation of Chagas disease in immunocompromised individuals, a key point for transplantation and HIV infection management. PMID:25077613

  13. Efficacy of Lychnopholide Polymeric Nanocapsules after Oral and Intravenous Administration in Murine Experimental Chagas Disease.

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    de Mello, Carlos Geraldo Campos; Branquinho, Renata Tupinambá; Oliveira, Maykon Tavares; Milagre, Matheus Marques; Saúde-Guimarães, Dênia Antunes; Mosqueira, Vanessa Carla Furtado; Lana, Marta de

    2016-09-01

    The etiological treatment of Chagas disease remains neglected. The compounds available show several limitations, mainly during the chronic phase. Lychnopholide encapsulated in polymeric nanocapsules (LYC-NC) was efficacious in mice infected with Trypanosoma cruzi and treated by intravenous administration during the acute phase (AP). As the oral route is preferred for treatment of chronic infections, such as Chagas disease, this study evaluated the use of oral LYC-NC in the AP and also compared it with LYC-NC administered to mice by the oral and intravenous routes during the chronic phase (CP). The therapeutic efficacy was evaluated by fresh blood examination, hemoculture, PCR, and enzyme-linked immunosorbent assay (ELISA). The cure rates in the AP and CP were 62.5% and 55.6%, respectively, upon oral administration of LYC-poly(d,l-lactide)-polyethylene glycol nanocapsules (LYC-PLA-PEG-NC) and 57.0% and 30.0%, respectively, with LYC-poly-ε-caprolactone nanocapsules (LYC-PCL-NC). These cure rates were significantly higher than that of free LYC, which did not cure any animals. LYC-NC formulations administered orally during the AP showed cure rates similar to that of benznidazole, but only LYC-NC cured mice in the CP. Similar results were achieved with intravenous treatment during the CP. The higher cure rates obtained with LYC loaded in PLA-PEG-NC may be due to the smaller particle size of these NC and the presence of PEG, which influence tissue diffusion and the controlled release of LYC. Furthermore, PLA-PEG-NC may improve the stability of the drug in the gastrointestinal tract. This work is the first report of cure of experimental Chagas disease via oral administration during the CP. These findings represent a new and important perspective for oral treatment of Chagas disease. Copyright © 2016, American Society for Microbiology. All Rights Reserved.

  14. Acute Chagas' cardiopathy in a polar bear (Ursus maritimus in Guadalajara, Mexico

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    Jaime-Andrade G. J.

    1997-01-01

    Full Text Available We report a 24 year old female polar bear (Ursus maritimus who contracted Chagas' infection at the Guadalajara Zoo, in Jalisco, México, and died of acute Chagas' carditis 15 days later. The histopathological findings are described, as well as the presence of triatomines (Triatoma longipennis Usinger infected with Trypanosoma cruzi collected within 5 meters from the place where the animal lived in the city of Guadalajara.

  15. Trypanosoma cruzi: experimental Chagas' disease in Rhesus monkeys. II. Ultraestructural and cytochemical studies of peroxidase and acid phosphatase activities

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    Maria de Nazareth Leal de Meirelles

    1990-06-01

    Full Text Available Ultrastructural and cytochemical studies of peroxidase and acid phosphatase were performed in skin, lymph node and heart muscle tissue of thesus monkeys with experimental Chagas's disease. At the site of inoculation ther was a proliferative reaction with the presence of immature macrophages revealed by peroxidase technique. At the lymph node a difuse inflammatory exudate with mononuclear cells, fibroblasts and immature activated macrophages reproduces the human patrtern of acute Chagas' disease inflamatory lesions. The hearth muscle cells present different degrees of degenerative alterations and a striking increase in the number of lysosomal profiles that exhibit acid hydrolase reaction product. A strong inflammatory reaction was present due to lymphocytic infiltrate or due to eosinophil granulocytes associated to ruptured cells. The present study provides some experimental evidences that the monkey model could be used as a reliable model to characterize histopathological alterations of the human disease.

  16. Outbreak of acute Chagas disease associated with oral transmission in the Rio Negro region, Brazilian Amazon.

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    Souza-Lima, Rita de Cássia de; Barbosa, Maria das Graças Vale; Coura, José Rodrigues; Arcanjo, Ana Ruth Lima; Nascimento, Adelaide da Silva; Ferreira, João Marcos Bemfica Barbosa; Magalhães, Laylah Kelre; Albuquerque, Bernardino Cláudio de; Araújo, Guilherme Alfredo Novelino; Guerra, Jorge Augusto de Oliveira

    2013-01-01

    Chagas disease is considered as emerging in the Brazilian Amazon, usually occurring in acute outbreaks. We describe 17 cases of acute Chagas disease in Rio Negro, Amazonas. There were 15 males (average age, 31.3 years), all positive for Trypanosoma cruzi in fresh blood smear examination, and 14 positive by xenodiagnosis and PCR. The top clinical manifestations were fever, asthenia, abdominal pain, and palpitations. Electrocardiograms featured low-voltage QRS, anterosuperior divisional block, and right bundle branch block associated with anterosuperior divisional block. All patients had consumed açaí products from Monte Alegre in the rural area around Santa Izabel do Rio Negro, Brazil.

  17. Cardiac beta-receptors in experimental Chagas' disease Receptores beta cardíacos na doença de Chagas experimental

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    Julio E. Enders

    1995-02-01

    Full Text Available Experimental Chagas' disease (45 to 90 days post-infection showed serious cardiac alterations in the contractility and in the pharmacological response to beta adrenergic receptors in normal and T. cruzi infected mice (post-acute phase. Chagasic infection did not change the beta receptors density (78.591 ± 3.125 fmol/mg protein and 73.647 ± 2.194 fmol/mg protein for controls but their affinity was significantly diminished (Kd = 7.299 ± 0.426 nM and Kd = 3.759 ± 0.212 nM for the control p Estudaram-se os receptores beta cardíacos de camundongos infectados pelo Trypanosoma cruzi na fase pós-aguda da doença de Chagas para estabelecer em que medida os mesmos contribuem a gerar respostas anômalas às catecolaminas observadas nestes miocardios. Utilizara-se 3-H/DHA para a marcação dos receptores beta cardíacos dos camundongos normais e dos infectados na fase pós-aguda (45 a 90 dias pós-infecção. O número dos sítios de fixação foi similar nos dois grupos, 78.591 ± 3.125 fmol/mg. Proteína nos chagásicos e 73.647 ± 2.194 fmol/mg. Proteína no grupo controle. Em vez disso, a afinidade verificou-se significativamente diminuida no grupo chagásico (Kd = 7.299 ± 0.426 nM respeito do controle (Kd = 3.759 ± 0.212 nM p < 0.001. Os resultados obtidos demonstram que as modificações observadas na estimulação adrenérgica do miocárdio chagásico se correlacionam com a menor afinidade dos receptores beta cardíacos e que estas alterações exerceriam uma parte determinante para as consequências funcionais que são detectadas na fase crônica.

  18. Benznidazole and posaconazole in experimental Chagas disease: positive interaction in concomitant and sequential treatments.

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    Lívia de Figueiredo Diniz

    Full Text Available Current chemotherapy for Chagas disease is unsatisfactory due to its limited efficacy, particularly in the chronic phase, with frequent side effects that can lead to treatment discontinuation. Combined therapy is envisioned as an ideal approach since it may improve treatment efficacy whilst decreasing toxicity and the likelihood of resistance development. We evaluated the efficacy of posaconazole in combination with benznidazole on Trypanosoma cruzi infection in vivo.Benznidazole and posaconazole were administered individually or in combination in an experimental acute murine infection model. Using a rapid treatment protocol for 7 days, the combined treatments were more efficacious in reducing parasitemia levels than the drugs given alone, with the effects most evident in combinations of sub-optimal doses of the drugs. Subsequently, the curative action of these drug combinations was investigated, using the same infection model and 25, 50, 75 or 100 mg/kg/day (mpk of benznidazole in combination with 5, 10 or 20 mpk of posaconazole, given alone or concomitantly for 20 days. The effects of the combination treatments on parasitological cures were higher than the sum of such effects when the drugs were administered separately at the same doses, indicating synergistic activity. Finally, sequential therapy experiments were carried out with benznidazole or posaconazole over a short interval (10 days, followed by the second drug administered for the same period of time. It was found that the sequence of benznidazole (100 mpk followed by posaconazole (20 mpk provided cure rates comparable to those obtained with the full (20 days treatments with either drug alone, and no cure was observed for the short treatments with drugs given alone.Our data demonstrate the importance of investigating the potential beneficial effects of combination treatments with marketed compounds, and showed that combinations of benznidazole with posaconazole have a positive

  19. Rescue Therapy with Nifurtimox and Dipyridamole for Severe Acute Chagas Myocarditis with Congestive Heart Failure in NMRI Albino Mice

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    Aparicio, Daniela Yustiz; González-Hernández, María; Hernández-Forero, Greybis; Guédez-Ortiz, María; Santeliz, Sonia; Goncalves, Loredana; Cabarcas, Rafael Bonfante

    2017-01-01

    Abstract Background: Chagas disease is a global health problem; therefore, the development of new therapeutic protocols is necessary. Our group recently demonstrated that nifurtimox associated with dipyridamole has curative effects in mice with acute Chagas disease. In this study, we assess the effect of this therapeutic protocol in chagasic mice with heart failure. Objective: To evaluate whether nifurtimox and dipyridamole are useful to rescue mice with severe acute chagasic myocarditis wi...

  20. Outbreak of acute Chagas disease associated with oral transmission in the Rio Negro region, Brazilian Amazon

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    Rita de Cássia de Souza-Lima

    2013-10-01

    Full Text Available Introduction Chagas disease is considered as emerging in the Brazilian Amazon, usually occurring in acute outbreaks. Methods We describe 17 cases of acute Chagas disease in Rio Negro, Amazonas. Results There were 15 males (average age, 31.3 years, all positive for Trypanosoma cruzi in fresh blood smear examination, and 14 positive by xenodiagnosis and PCR. The top clinical manifestations were fever, asthenia, abdominal pain, and palpitations. Electrocardiograms featured low-voltage QRS, anterosuperior divisional block, and right bundle branch block associated with anterosuperior divisional block. Conclusions All patients had consumed açaí products from Monte Alegre in the rural area around Santa Izabel do Rio Negro, Brazil.

  1. Outbreak of acute Chagas disease associated with oral transmission in the Rio Negro region, Brazilian Amazon

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    Rita de Cassia de Souza-Lima

    2013-07-01

    Full Text Available Introduction Chagas disease is considered as emerging in the Brazilian Amazon, usually occurring in acute outbreaks. Methods We describe 17 cases of acute Chagas disease in Rio Negro, Amazonas. Results There were 15 males (average age, 31.3 years, all positive for Trypanosoma cruzi in fresh blood smear examination, and 14 positive by xenodiagnosis and PCR. The top clinical manifestations were fever, asthenia, abdominal pain, and palpitations. Electrocardiograms featured low-voltage QRS, anterosuperior divisional block, and right bundle branch block associated with anterosuperior divisional block. Conclusions All patients had consumed açaí products from Monte Alegre in the rural area around Santa Izabel do Rio Negro, Brazil.

  2. [Investigation of vectors and reservoirs in an acute Chagas outbreak due to possible oral transmission in Aguachica, Cesar, Colombia].

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    Soto, Hugo; Tibaduiza, Tania; Montilla, Marleny; Triana, Omar; Suárez, Diana Carolina; Torres Torres, Mariela; Arias, María Teresa; Lugo, Ligia

    2014-04-01

    Colombia recorded 11 cases of acute Chagas disease and 80 cases of oral contamination with Trypanosoma cruzi. The current study analyzes the entomological and parasitological characteristics of the outbreak in Aguachica, Cesar Department, in 2010. An interdisciplinary group of health professionals and regional university personnel conducted the laboratory tests in the patients and the investigation of the transmission focus. Eleven cases of acute Chagas diseases were detected in a single family in a dwelling with domiciliated triatomines and Rhodnius pallescens, Pantrongylus geniculatus, Eratyrus cuspidatus, and two Didelphis marsupialis opossums infected with T. cruzi in Attalea butyracea and Elaeis oleifera palm trees in the urban area of Aguachica. The study analyzes the role of R. pallescens and palm trees in the wild cycle of T. cruzi and in oral transmission of Chagas disease. Sporadic incursions by wild R. pallescens, P. geniculatus, and E. cuspidatus from the nearby palm trees into human dwellings may cause increasingly frequent outbreaks of oral Chagas disease.

  3. Uneventful benznidazole treatment of acute Chagas disease during pregnancy: a case report

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    Valeria Rita Corrêa

    2014-06-01

    Full Text Available This report describes the case of a patient with acute Chagas disease in Tocantins, Brazil, who was unaware of her pregnancy during benznidazole treatment. She presented with impaired cardiac function during the acute phase (pericarditis and incomplete right bundle-branch block that resolved favorably after benznidazole therapy. Serological results also became negative, as determined by hemagglutination assays, enzyme-linked immunosorbent assays, and immunofluorescence assays. The child was born without sequelae and showed no evidence of congenital Trypanosoma cruzi infection at birth or 24 days later.

  4. FIRST REPORT OF ACUTE CHAGAS DISEASE BY VECTOR TRANSMISSION IN RIO DE JANEIRO STATE, BRAZIL

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    Luiz Henrique Conde SANGENIS

    2015-08-01

    Full Text Available SUMMARY Chagas disease (CD is an endemic anthropozoonosis from Latin America of which the main means of transmission is the contact of skin lesions or mucosa with the feces of triatomine bugs infected by Trypanosoma cruzi. In this article, we describe the first acute CD case acquired by vector transmission in the Rio de Janeiro State and confirmed by parasitological, serological and PCR tests. The patient presented acute cardiomyopathy and pericardial effusion without cardiac tamponade. Together with fever and malaise, a 3 cm wide erythematous, non-pruritic, papule compatible with a "chagoma" was found on his left wrist. This case report draws attention to the possible transmission of CD by non-domiciled native vectors in non-endemic areas. Therefore, acute CD should be included in the diagnostic workout of febrile diseases and acute myopericarditis in Rio de Janeiro.

  5. Benznidazole/Itraconazole Combination Treatment Enhances Anti-Trypanosoma cruzi Activity in Experimental Chagas Disease.

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    Tassiane Assíria Fontes Martins

    Full Text Available The nitroheterocyclic drugs nifurtimox and benznidazole are first-line drugs available to treat Chagas disease; however, they have limitations, including long treatment courses and toxicity. Strategies to overcome these limitations include the identification of new drugs with specific target profiles, re-dosing regimens for the current drugs, drug repositioning and combination therapy. In this work, we evaluated combination therapy as an approach for optimization of the current therapeutic regimen for Chagas disease. The curative action of benznidazole/itraconazole combinations was explored in an established infection of the mice model with the T. cruzi Y strain. The activities of the benznidazole/itraconazole combinations were compared with the results from those receiving the same dosage of each individual drug. The administration of benznidazole/itraconazole in combination eliminated parasites from the blood more efficiently than each drug alone. Here, there was a significant reduction of the number of treatment days (number of doses necessary to induce parasitemia suppression with the benznidazole/itraconazole combination, as compared to each compound administered alone. These results clearly indicate the enhanced effects of these drugs in combination, particularly at the dose of 75 mg/kg, as the effects observed with the drug combinations were four times more effective than those of each drug used alone. Moreover, benznidazole/itraconazole treatment was shown to prevent or decrease the typical lesions associated with chronic experimental Chagas disease, as illustrated by similar levels of inflammatory cells and fibrosis in the cardiac muscle tissue of healthy and treated mice. These results emphasize the importance of exploring the potential of combination treatments with currently available compounds to specifically treat Chagas disease.

  6. Benznidazole/Itraconazole Combination Treatment Enhances Anti-Trypanosoma cruzi Activity in Experimental Chagas Disease.

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    Assíria Fontes Martins, Tassiane; de Figueiredo Diniz, Lívia; Mazzeti, Ana Lia; da Silva do Nascimento, Álvaro Fernando; Caldas, Sérgio; Caldas, Ivo Santana; de Andrade, Isabel Mayer; Ribeiro, Isabela; Bahia, Maria Terezinha

    2015-01-01

    The nitroheterocyclic drugs nifurtimox and benznidazole are first-line drugs available to treat Chagas disease; however, they have limitations, including long treatment courses and toxicity. Strategies to overcome these limitations include the identification of new drugs with specific target profiles, re-dosing regimens for the current drugs, drug repositioning and combination therapy. In this work, we evaluated combination therapy as an approach for optimization of the current therapeutic regimen for Chagas disease. The curative action of benznidazole/itraconazole combinations was explored in an established infection of the mice model with the T. cruzi Y strain. The activities of the benznidazole/itraconazole combinations were compared with the results from those receiving the same dosage of each individual drug. The administration of benznidazole/itraconazole in combination eliminated parasites from the blood more efficiently than each drug alone. Here, there was a significant reduction of the number of treatment days (number of doses) necessary to induce parasitemia suppression with the benznidazole/itraconazole combination, as compared to each compound administered alone. These results clearly indicate the enhanced effects of these drugs in combination, particularly at the dose of 75 mg/kg, as the effects observed with the drug combinations were four times more effective than those of each drug used alone. Moreover, benznidazole/itraconazole treatment was shown to prevent or decrease the typical lesions associated with chronic experimental Chagas disease, as illustrated by similar levels of inflammatory cells and fibrosis in the cardiac muscle tissue of healthy and treated mice. These results emphasize the importance of exploring the potential of combination treatments with currently available compounds to specifically treat Chagas disease.

  7. Elevated environmental temperature enhances immunity in experimental Chagas' disease.

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    Anderson, K J; Kuhn, R E

    1989-01-01

    C3H mice are highly susceptible to the Brazil strain of Trypanosoma cruzi. These mice usually die during the acute phase of infection and develop a profound immunosuppression to heterologous and parasite antigen. In this study, we confirmed earlier reports that infected mice maintained at elevated environmental temperature (36 degrees C) are significantly more resistant to T. cruzi than are mice kept at 20 to 24 degrees C. To determine whether the benefits of increased environmental temperature were due to alterations in the host immune system, the production of antibody to heterologous antigen and the development of parasite-specific T-helper cells were examined in noninfected and T. cruzi-infected mice. Mice were immunized with either sheep erythrocytes (SRBC) or trinitrophenyl groups (TNP) conjugated to fixed culture forms of T. cruzi, and the splenic direct plaque-forming cell (DPFC) responses to SRBC and to TNP-conjugated SRBC were determined. The DPFC response to SRBC from infected mice maintained at elevated environmental temperature was much higher than the suppressed response of infected mice held at room temperature and slightly higher than the response of age-matched noninfected control mice. Likewise, maintaining infected mice at 36 degrees C significantly enhanced the parasite-specific responses of T-helper cells, as reflected by anti-TNP DPFC responses of mice immunized with TNP-conjugated TC.

  8. Different infective forms trigger distinct immune response in experimental Chagas disease.

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    Paula Melo de Abreu Vieira

    Full Text Available Although metacyclic and blood trypomastigotes are completely functional in relation to parasite-host interaction and/or target cell invasion, they differ in the molecules present on the surface. Thus, aspects related to the variability that the forms of T. cruzi interacts with host cells may lead to fundamental implications on the immune response against this parasite and, consequently, the clinical evolution of Chagas disease. We have shown that BT infected mice presented higher levels of parasitemia during all the acute phase of infection. Moreover, the infection with either MT or BT forms resulted in increased levels of total leukocytes, monocytes and lymphocytes, specifically later for MT and earlier for BT. The infection with BT forms presented earlier production of proinflammatory cytokine TNF-α and later of IFN-γ by both T cells subpopulations. This event was accompanied by an early cardiac inflammation with an exacerbation of this process at the end of the acute phase. On the other hand, infection with MT forms result in an early production of IFN-γ, with subsequent control in the production of this cytokine by IL-10, which provided to these animals an immunomodulatory profile in the end of the acute phase. These results are in agreement with what was found for cardiac inflammation where animals infected with MT forms showed intense cardiac inflammation later at infection, with a decrease in the same at the end of this phase. In summary, our findings emphasize the importance of taking into account the inoculums source of T. cruzi, since vectorial or transfusional routes of T. cruzi infection may trigger distinct parasite-host interactions during the acute phase that may influence relevant biological aspects of chronic Chagas disease.

  9. Different Infective Forms Trigger Distinct Immune Response in Experimental Chagas Disease

    Science.gov (United States)

    Vieira, Paula Melo de Abreu; Francisco, Amanda Fortes; Machado, Evandro Marques de Meneses; Nogueira, Nívia Carolina; Fonseca, Kátia da Silva; Reis, Alexandre Barbosa; Teixeira-Carvalho, Andrea; Martins-Filho, Olindo Assis; Tafuri, Washington Luiz; Carneiro, Cláudia Martins

    2012-01-01

    Although metacyclic and blood trypomastigotes are completely functional in relation to parasite-host interaction and/or target cell invasion, they differ in the molecules present on the surface. Thus, aspects related to the variability that the forms of T. cruzi interacts with host cells may lead to fundamental implications on the immune response against this parasite and, consequently, the clinical evolution of Chagas disease. We have shown that BT infected mice presented higher levels of parasitemia during all the acute phase of infection. Moreover, the infection with either MT or BT forms resulted in increased levels of total leukocytes, monocytes and lymphocytes, specifically later for MT and earlier for BT. The infection with BT forms presented earlier production of proinflammatory cytokine TNF-α and later of IFN-γ by both T cells subpopulations. This event was accompanied by an early cardiac inflammation with an exacerbation of this process at the end of the acute phase. On the other hand, infection with MT forms result in an early production of IFN-γ, with subsequent control in the production of this cytokine by IL-10, which provided to these animals an immunomodulatory profile in the end of the acute phase. These results are in agreement with what was found for cardiac inflammation where animals infected with MT forms showed intense cardiac inflammation later at infection, with a decrease in the same at the end of this phase. In summary, our findings emphasize the importance of taking into account the inoculums source of T. cruzi, since vectorial or transfusional routes of T. cruzi infection may trigger distinct parasite-host interactions during the acute phase that may influence relevant biological aspects of chronic Chagas disease. PMID:22412949

  10. Inoculação experimental de Equus asinus com Leishmania chagasi Cunha & Chagas, 1937 Experimental infection of Equus asinus with Leishmania chagasi Cunha & Chagas, 1937

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    Elúzio José Lima Cerqueira

    2003-12-01

    Full Text Available Quatro Equus asinus foram inoculados com promastigotas de Leishmania chagasi Cunha & Chagas, 1937 e acompanhados durante 12 meses através de: pesquisa de amastigotas em esfregaços e culturas de sangue periférico em fragmentos de tecido do lábio inferior, medula óssea, baço e fígado e de testes de ELISA e TRALd. Estes foram positivos nos 8º, 10º e 12º meses após a inoculação. O exame histopatológico pós necropsia, demonstrou discreto número de amastigotas no fígado de dois dos eqüídeos inoculados. Apesar de desafiados com elevado número de promastigotas, os animais não desenvolveram infecções patentes e não infectaram experimentalmente a vetora Lutzomya longipalpis. Os resultados induzem a acreditar que os eqüídeos são desprovidos de importância como reservatórios na cadeia de transmissão da leishmaniose visceral, embora sirvam como boa fonte de alimentação sangüínea e proliferação da vetora Lutzomyia longipalpis.Four Equus asinus were challenged with promastigotes of Leishmania chagasi Cunha & Chagas, 1937, and followed up for 12 months. They were observed by means of direct testing for promastigotes in smears and culture of peripheral blood, fragments from inferior lip, bone marrow, spleen and liver and the immunological assays ELISA and TRALd. The post-necropsy histological examination demonstrated a small number of amastigotes in the liver of two animals. ELISA and TRALd tests were positive at the 8th, 10th and 12th month after inoculation. The results suggest that the donkeys were able to overcome the experimental leishmanial infection and did not infect the vector Lutzomyia longipalpis in the laboratory. Consequently they can not be considered an important reservoir in the epidemiological chain of transmission of visceral leishmaniasis, although they represent an important blood source for the vector and its proliferation.

  11. [Chagas disease].

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    Develoux, M; Lescure, F-X; Le Loup, G; Pialoux, G

    2009-08-01

    Chagas disease (human American trypanosomiasis) is a zoonose caused by the protozoan Trypanosoma cruzi. Vectors are Triatoma spp. insects. T. cruzi can also be transmitted by blood transfusion, organ transplantation, and transplacentally. Infection is generally acquired during infancy. The acute infection is rarely symptomatic and is followed by a chronic phase. Chronic infected people are asymptomatic (indeterminate stage) and may remain at this stage for the rest of their lives. About a third of infected people will develop a chronic Chagas disease which affects the heart and the digestive tract. Morbidity and mortality of chronic Chagas cardiomyopathy (CCC) are high. Specific treatment of asymptomatic infected individual could reduce the risk of progression to CCC. With control initiatives case incidence declined in most endemic countries. American trypanosomiasis has become an emerging imported disease in North America and Europe because of the migration of population originating from endemic zones. They are only two available drugs for specific treatment of Chagas disease: benznidazole and nifurtimox. Both have frequent side effects and variable efficacy according the phase of the disease. There is an urgent need for new treatments and better serological tests. Policies must be developed to avoid the risk of transmission trough blood transfusion and transplantation in developed countries.

  12. Treatment with low doses of aspirin during chronic phase of experimental Chagas' disease increases oesophageal nitrergic neuronal subpopulation in mice.

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    Massocatto, Cristina Lorena; Martins Moreira, Neide; Muniz, Eliane; Marques de Araújo, Silvana; Pinge-Filho, Phileno; Rossi, Robson Marcelo; de Almeida Araújo, Eduardo José; de Mello Gonçales Sant'ana, Débora

    2018-01-19

    Patients with Chagas' disease may develop dysfunctions of oesophageal and colonic motility resulting from the degeneration or loss of the myenteric neurons of the enteric nervous system. Studies have shown that the use of aspirin, also known as acetylsalicylic acid (ASA), influences the pathogenesis of the disease. However, this remains controversial. The aim of this study was to evaluate the consequences of treatment with low doses of aspirin during the chronic phase of Chagas' disease on oesophageal function. Twenty male Swiss mice, 60 days of age, were used. The animals were infected with Y strain of Trypanosoma cruzi, injected intraperitoneally. Aspirin was given at a dose of 50 mg/kg to some of the infected animals, from the 55th to 63rd day after inoculation on consecutive days, and from the 65th to 75th day on alternate days. We investigated food passage of time, wall structure and nitrergic neuronal population of the distal oesophagus. Our data revealed that the use of low doses of aspirin in chronic Chagas' disease caused an increase in the number of nitrergic neurons and partially prevented hypertrophy of the oesophagus. In addition, the aspirin administration impeded Chagas' diseases associated changes in intestinal transit time. Thus treatment with aspirin in the chronic phase of Chagas' disease changes the natural history of the disease and raises the possibility of using it as a new therapeutic approach to the treatment of this aspect of Chagas' disease pathology. © 2018 The Authors. International Journal of Experimental Pathology © 2018 International Journal of Experimental Pathology.

  13. Sesquiterpene lactone in nanostructured parenteral dosage form is efficacious in experimental Chagas disease.

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    Branquinho, Renata Tupinambá; Mosqueira, Vanessa Carla Furtado; de Oliveira-Silva, Jaquelline Carla Valamiel; Simões-Silva, Marianne Rocha; Saúde-Guimarães, Dênia Antunes; de Lana, Marta

    2014-01-01

    The drugs available for Chagas disease treatment are toxic and ineffective. We studied the in vivo activity of a new drug, lychnopholide (LYC). LYC was loaded in nanocapsules (NC), and its effects were compared to free LYC and benznidazole against Trypanosoma cruzi. Infected mice were treated in the acute phase at 2.0 mg/kg/day with free LYC, LYC-poly-ε-caprolactone NC (LYC-PCL), and LYC-poly(lactic acid)-co-polyethylene glycol NC (LYC-PLA-PEG) or at 50 mg/kg/day with benznidazole solution by the intravenous route. Animals infected with the CL strain, treated 24 h after infection for 10 days, evaluated by hemoculture, PCR, and enzyme-linked immunosorbent assay exhibited a 50% parasitological cure when treated with LYC-PCL NC and 100% cure when treated with benznidazole, but 100% of the animals treated during the prepatent period for 20 days with these formulations or LYC-PLA-PEG NC were cured. In animals with the Y strain treated 24 h after infection for 10 days, only mice treated by LYC-PCL NC were cured, but animals treated in the prepatent period for 20 days exhibited 100, 75, and 62.5% cure when treated with LYC-PLA-PEG NC, benznidazole, and LYC-PCL NC, respectively. Free LYC reduced the parasitemia and improved mice survival, but no mice were cured. LYC-loaded NC showed higher cure rates, reduced parasitemia, and increased survival when used in doses 2five times lower than those used for benznidazole. This study confirms that LYC is a potential new treatment for Chagas disease. Furthermore, the long-circulating property of PLA-PEG NC and its ability to improve LYC efficacy showed that this formulation is more effective in reaching the parasite in vivo.

  14. An experimental and clinical assay with ketoconazole in the treatment of Chagas disease

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    Zigman Brener

    1993-03-01

    Full Text Available Ketoconazole an azole antifungic drug which is already in the market has also been demonstrated to be active against Trypanossoma cruzi experimental infections. In this paper we confirmed the drug effect and investigated its range of activity against different T. cruzi strains naturally resistant or susceptible to both standard drugs Nifurtimox and Benznidazole used clinically in Chagas disease. Moreover, we have shown that the association of Ketoconazole plus Lovastatin (an inhibitor of sterol synthesis, which has an antiproliferative effect against T. cruzi in vitro, failed to enhance the supressive effect of Ketoconazole displayed when administered alone to infected mice. Finally, administration in chronic chagasic patients of Ketoconazole at doses used in the treatment of deep mycosis also failed to induce cure as demonstrated by parasitological and serological tests. The strategy of identify and test drugs which are already in the market and fortuitously are active against T. cruzi has been discussed.

  15. Acute Chagas outbreaks: molecular and biological features of Trypanosoma cruzi isolates, and clinical aspects of acute cases in Santander, Colombia.

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    Díaz, Martha Lucía; Leal, Sandra; Mantilla, Julio César; Molina-Berríos, Alfredo; López-Muñoz, Rodrigo; Solari, Aldo; Escobar, Patricia; González Rugeles, Clara Isabel

    2015-11-26

    Outbreaks of acute Chagas disease associated with oral transmission are easily detected nowadays with trained health personnel in areas of low endemicity, or in which the vector transmission has been interrupted. Given the biological and genetic diversity of Trypanosoma cruzi, the high morbidity, mortality, and the observed therapeutic failure, new characteristics of these outbreaks need to be addressed at different levels, both in Trypanosoma cruzi as in patient response. The aim of this work was to evaluate the patient's features involved in six outbreaks of acute Chagas disease which occurred in Santander, Colombia, and the characteristics of Trypanosoma cruzi clones isolated from these patients, to establish the potential relationship between the etiologic agent features with host behavior. The clinical, pathological and epidemiological aspects of outbreaks were analyzed. In addition, Trypanosoma cruzi clones were biologically characterized both in vitro and in vivo, and the susceptibility to the classical trypanocidal drugs nifurtimox and benznidazole was evaluated. Trypanosoma cruzi clones were genotyped by means of mini-exon intergenic spacer and cytochrome b genes sequencing. All clones were DTU I, and based on the mini-exon intergenic spacer, belong to two genotypes: G2 related with sub-urban, and G11 with rural outbreaks. Girón outbreak clones with higher susceptibility to drugs presented G2 genotype and C/T transition in Cyt b. The outbreaks affected mainly young population (±25.9 years), and the mortality rate was 10 %. The cardiac tissue showed intense inflammatory infiltrate, myocardial necrosis and abundant amastigote nests. However, although the gastrointestinal tissue was congestive, no inflammation or parasites were observed. Although all clones belong to DTU I, two intra-DTU genotypes were found with the sequencing of the mini-exon intergenic spacer, however there is no strict correlation between genetic groups, the cycles of the parasite or

  16. Treatment with Fenofibrate plus a low dose of Benznidazole attenuates cardiac dysfunction in experimental Chagas disease

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    Ágata C. Cevey

    2017-12-01

    Full Text Available Trypanosoma cruzi induces serious cardiac alterations during the chronic infection. Intense inflammatory response observed from the beginning of infection, is critical for the control of parasite proliferation and evolution of Chagas disease. Peroxisome proliferator-activated receptors (PPAR-α, are known to modulate inflammation.In this study we investigated whether a PPAR-α agonist, Fenofibrate, improves cardiac function and inflammatory parameters in a murine model of T. cruzi infection. BALB/c mice were sequentially infected with two T. cruzi strains of different genetic background. Benznidazole, commonly used as trypanocidal drug, cleared parasites but did not preclude cardiac pathology, resembling what is found in human chronic chagasic cardiomyopathy. Fenofibrate treatment restored to normal values the ejection and shortening fractions, left ventricular end-diastolic, left ventricular end-systolic diameter, and isovolumic relaxation time. Moreover, it reduced cardiac inflammation and fibrosis, decreased the expression of pro-inflammatory (IL-6, TNF-α and NOS2 and heart remodeling mediators (MMP-9 and CTGF, and reduced serum creatine kinase activity. The fact that Fenofibrate partially inhibited NOS2 expression and NO release in the presence of a PPAR-α non-competitive inhibitor, suggested it also acted through PPAR-α-independent pathways. Since IκBα cytosolic degradation was inhibited by Fenofibrate, it can be concluded that the NFκB pathway has a role in its effects. Thus, we demonstrate that Fenofibrate acts through PPAR-α-dependent and -independent pathways.Our study shows that combined treatment with Fenofibrate plus Benznidazole is able both to reverse the cardiac dysfunction associated with the ongoing inflammatory response and fibrosis and to attain parasite clearance in an experimental model of Chagas disease. Keywords: Trypanosoma cruzi, Heart dysfunction, PPAR-α, Fenofibrate treatment, Inflammatory

  17. Increase of reactive oxygen species by desferrioxamine during experimental Chagas' disease

    Science.gov (United States)

    Francisco, Amanda Fortes; de Abreu Vieira, Paula Melo; Arantes, Jerusa Marilda; Silva, Maisa; Pedrosa, Maria Lúcia; Elói-Santos, Silvana Maria; Martins-Filho, Olindo Assis; Teixeira-Carvalho, Andréa; Araújo, Márcio Sobreira Silva; Tafuri, Washington Luiz; Carneiro, Cláudia Martins

    2010-01-01

    Oxidative stress is common in inflammatory processes associated with many diseases including Chagas' disease. The aim of the present study was to evaluate, in a murine model, biomarkers of oxidative stress together with components of the antioxidant system in order to provide an overview of the mechanism of action of the iron chelator desferrioxamine (DFO). The study population comprised 48 male Swiss mice, half of which were treated daily by intraperitoneal injection of DFO over a 35-day period, while half were administered sterile water in a similar manner. On the 14th day of the experiment, 12 DFO-treated mice and an equal number of untreated mice were experimentally infected with Trypanosoma cruzi. Serum concentrations of nitric oxide and superoxide dismutase and hepatic levels of total glutathione, thiobarbituric acid reactive species and protein carbonyl, were determined on days 0, 7, 14 and 21 post-infection. The results obtained revealed that DFO enhances antioxidant activity in the host but also increases oxidative stress, indicating that the mode of action of the drug involves a positive contribution to the host together with an effect that is not beneficial to the parasite. PMID:20663295

  18. Megabladder in experimental Chagas disease: pathological features of the bladder wall Mega bexiga na Doença de Chagas experimental. Caracteristicas patológicas da parede vesical

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    Luciano Henrique Gazoni Scremin

    1999-04-01

    Full Text Available Mega-organs, primarily in the digestive tract, are well known to occur in chronic Chagas disease. Acute experimental infection with Trypanosoma cruzi results in parasitism of a wide range of cells, tissues, and organs, including the urinary bladder. Infection of BALB/c mice with 100,000 bloodstream forms of the Y strain of T. cruzi induced acute infection with intense parasitism of all layers of the urinary bladder. Parasites were found in the mucosa, lamina propria, muscular, adventitial connective, and fat tissue. Desquamate epithelial cells with amastigotes in the bladder lumen were also found. After 60 days of infection, mice inoculated with 50 bloodstream forms developed dilated, thin-walled bladders that had inflammatory infiltrates and foci of fibrosis replacing areas of damaged muscular layer. These lesions result from direct damage to the muscle fibers by the T. cruzi, leading to myosites, muscle damage, and scarring. Direct damage of paraganglia cells secondary to parasitism, leading to dilatation, damage of muscle fibers, and scarring with replacement of muscular tissue with connective tissue, should also be considered as a cause of functional disturbance of the urinary bladder.Os "mega-órgãos" na Doença de Chagas são bem conhecidos, especialmente os desenvolvidos no sistema digestivo. A infecção aguda apresenta parasitismo de diversas células, tecidos e órgãos, dentre eles a bexiga urinária. Camundongos Balb/c infectados com 100.000 formas sanguíneas de cepa Y de T. cruzi mostraram intenso parasitismo de todas camadas da bexiga urinária na fase aguda. Os parasitas foram encontrados na mucosa, submucosa, lâmina própria, muscular, adventícia e tecido adiposo, além das células descamadas para a luz do órgão. Para produzir a fase crônica, os animais foram inoculados com a mesma cepa, porém apenas inóculo com 50 formas sangüíneas. Após sessenta dias de infecção, detectamos dilatações da parede vesical, assim

  19. Experimental chemotherapy for Chagas disease: 15 years of research contributions from in vivo and in vitro studies

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    Maria de Nazaré C Soeiro

    2009-07-01

    Full Text Available Chagas disease, which is caused by the intracellular parasite Trypanosoma cruzi, is a neglected illness with 12-14 million reported cases in endemic geographic regions of Latin America. While the disease still represents an important public health problem in these affected areas, the available therapy, which was introduced more than four decades ago, is far from ideal due to its substantial toxicity, its limited effects on different parasite stocks, and its poor activity during the chronic phase of the disease. For the past 15 years, our group, in collaboration with research groups focused on medicinal chemistry, has been working on experimental chemotherapies for Chagas disease, investigating the biological activity, toxicity, selectivity and cellular targets of different classes of compounds on T. cruzi. In this report, we present an overview of these in vitro and in vivo studies, focusing on the most promising classes of compounds with the aim of contributing to the current knowledge of the treatment of Chagas disease and aiding in the development of a new arsenal of candidates with anti-T. cruzi efficacy.

  20. Chagas Disease

    Science.gov (United States)

    Chagas disease is caused by a parasite. It is common in Latin America but not in the United ... There are no vaccines or medicines to prevent Chagas disease. If you travel to areas where it occurs, ...

  1. [Series of acute Chagas' disease cases attended at a tertiary-level clinic in Manaus, State of Amazonas, from 1980 to 2006].

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    Monteiro, Wuelton Marcelo; Barbosa, Maria das Graças Vale; Toledo, Max Jean de Ornelas; Fé, Flávio Augusto; Fé, Nelson Ferreira

    2010-01-01

    Chagas disease is an emerging and neglected problem in the Brazilian Amazon region. This study describes a series of acute autochthonous cases of Chagas disease that were attended at the Tropical Medicine Foundation of Amazonas, Manaus, between 1980 and 2006. Twenty-nine cases were recorded: 19 (65.5%) were male and 10 (34.5%) cases were female. Fifteen (51.7%) were isolated cases and 14 (48.3%) were from outbreaks. The commonest signs and symptoms were fever, fatigue, headache, myalgia, chills, pallor, dyspnea and edema of the face and lower limbs. No deaths were recorded. The disease occurred frequently among young people. The parasitological methods showed high sensitivity.

  2. Molecular and serological detection of Trypanosoma cruzi in dogs (Canis lupus familiaris) suggests potential transmission risk in areas of recent acute Chagas disease outbreaks in Colombia.

    Science.gov (United States)

    Jaimes-Dueñez, Jeiczon; Triana-Chávez, Omar; Cantillo-Barraza, Omar; Hernández, Carolina; Ramírez, Juan David; Góngora-Orjuela, Agustín

    2017-06-01

    Chagas disease is a zoonotic infection widely distributed in tropical and subtropical regions of America, including more than 50% of the Colombian territory. In the last years, an increase of outbreaks of acute Chagas disease has been observed in the east of the country due to environmental changes and mammal movements toward human settlements. Given the importance of dogs (Canis lupus familiaris) as reservoir hosts and sentinels of Trypanosoma cruzi infection across different regions of America, in this study we reported a serological and molecular detection of T. cruzi infection in 242 dogs from an endemic area of Meta department (East of Colombia), with recent emergence of acute Chagas disease outbreaks. The distribution of T. cruzi infection in dogs was not homogeneous, ranging from 0-41.4% and 0-5.1% in different sampling sectors, through serological (ELISA/IFAT) and molecular methods (conventional and real time PCR), respectively. Statistical analysis indicated that dog infection was associated with specific sampling sectors. Our results show a moderate seroprevalence of infection and active circulation of T. cruzi in dogs from this zone, which suggest areas with potential risk of infection to human that must be taken into consideration when Chagas disease control programs need to be implemented. Copyright © 2017 Elsevier B.V. All rights reserved.

  3. Molecular Diagnosis of Chagas Disease in Colombia: Parasitic Loads and Discrete Typing Units in Patients from Acute and Chronic Phases

    Science.gov (United States)

    Hernández, Carolina; Cucunubá, Zulma; Flórez, Carolina; Olivera, Mario; Valencia, Carlos; Zambrano, Pilar; León, Cielo; Ramírez, Juan David

    2016-01-01

    Background The diagnosis of Chagas disease is complex due to the dynamics of parasitemia in the clinical phases of the disease. The molecular tests have been considered promissory because they detect the parasite in all clinical phases. Trypanosoma cruzi presents significant genetic variability and is classified into six Discrete Typing Units TcI-TcVI (DTUs) with the emergence of foreseen genotypes within TcI as TcIDom and TcI Sylvatic. The objective of this study was to determine the operating characteristics of molecular tests (conventional and Real Time PCR) for the detection of T. cruzi DNA, parasitic loads and DTUs in a large cohort of Colombian patients from acute and chronic phases. Methodology/Principal Findings Samples were obtained from 708 patients in all clinical phases. Standard diagnosis (direct and serological tests) and molecular tests (conventional PCR and quantitative PCR) targeting the nuclear satellite DNA region. The genotyping was performed by PCR using the intergenic region of the mini-exon gene, the 24Sa, 18S and A10 regions. The operating capabilities showed that performance of qPCR was higher compared to cPCR. Likewise, the performance of qPCR was significantly higher in acute phase compared with chronic phase. The median parasitic loads detected were 4.69 and 1.33 parasite equivalents/mL for acute and chronic phases. The main DTU identified was TcI (74.2%). TcIDom genotype was significantly more frequent in chronic phase compared to acute phase (82.1% vs 16.6%). The median parasitic load for TcIDom was significantly higher compared with TcI Sylvatic in chronic phase (2.58 vs.0.75 parasite equivalents/ml). Conclusions/Significance The molecular tests are a precise tool to complement the standard diagnosis of Chagas disease, specifically in acute phase showing high discriminative power. However, it is necessary to improve the sensitivity of molecular tests in chronic phase. The frequency and parasitemia of TcIDom genotype in chronic

  4. Involvement of the autonomic nervous system in Chagas heart disease

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    Edison Reis Lopes

    1983-12-01

    Full Text Available The autonomic nervous system and especially the intracardiac autonomic nervous system is involved in Chagas' disease. Ganglionitis and periganglionitis were noted in three groups ofpatients dying with Chagas'disease: 1 Those in heart failure; 2 Those dying a sudden, non violent death and; 3 Those dying as a consequence ofaccidents or homicide. Hearts in the threegroups also revealed myocarditis and scattered involvement of intramyocardial ganglion cells as well as lesions of myelinic and unmyelinic fibers ascribable to Chagas'disease. In mice with experimentally induced Chagas' disease weobserved more intensive neuronal lesions of the cardiac ganglia in the acute phase of infection. Perhaps neuronal loss has a role in the pathogenesis of Chagas cardiomyopathy. However based on our own experience and on other data from the literature we conclude that the loss of neurones is not the main factor responsible for the manifestations exhibited by chronic chagasic patients. On the other hand the neuronal lesions may have played a role in the sudden death ofone group of patients with Chagas'disease but is difficult to explain the group of patients who did not die sudderly but instead progressed to cardiac failure.

  5. Trypanosoma cruzi IV causing outbreaks of acute Chagas disease and infections by different haplotypes in the Western Brazilian Amazonia.

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    Wuelton Marcelo Monteiro

    Full Text Available BACKGROUND: Chagas disease is an emergent tropical disease in the Brazilian Amazon Region, with an increasing number of cases in recent decades. In this region, the sylvatic cycle of Trypanosoma cruzi transmission, which constitutes a reservoir of parasites that might be associated with specific molecular, epidemiological and clinical traits, has been little explored. The objective of this work is to genetically characterize stocks of T. cruzi from human cases, triatomines and reservoir mammals in the State of Amazonas, in the Western Brazilian Amazon. METHODOLOGY/PRINCIPAL FINDINGS: We analyzed 96 T. cruzi samples from four municipalities in distant locations of the State of Amazonas. Molecular characterization of isolated parasites from cultures in LIT medium or directly from vectors or whole human blood was performed by PCR of the non-transcribed spacer of the mini-exon and of the 24 S alfa ribosomal RNA gene, RFLP and sequencing of the mitochondrial cytochrome c oxidase subunit II (COII gene, and by sequencing of the glucose-phosphate isomerase gene. The T. cruzi parasites from two outbreaks of acute disease were all typed as TcIV. One of the outbreaks was triggered by several haplotypes of the same DTU. TcIV also occurred in isolated cases and in Rhodnius robustus. Incongruence between mitochondrial and nuclear phylogenies is likely to be indicative of historical genetic exchange events resulting in mitochondrial introgression between TcIII and TcIV DTUs from Western Brazilian Amazon. TcI predominated among triatomines and was the unique DTU infecting marsupials. CONCLUSION/SIGNIFICANCE: DTU TcIV, rarely associated with human Chagas disease in other areas of the Amazon basin, is the major strain responsible for the human infections in the Western Brazilian Amazon, occurring in outbreaks as single or mixed infections by different haplotypes.

  6. Serodiagnosis of Chronic and Acute Chagas' Disease with Trypanosoma cruzi Recombinant Proteins: Results of a Collaborative Study in Six Latin American Countries

    Science.gov (United States)

    Umezawa, Eufrosina S.; Luquetti, Alejandro O.; Levitus, Gabriela; Ponce, Carlos; Ponce, Elisa; Henriquez, Diana; Revollo, Susana; Espinoza, Bertha; Sousa, Octavio; Khan, Baldip; da Silveira, José Franco

    2004-01-01

    An enzyme-linked immunosorbent assay to diagnose Chagas' disease by a serological test was performed with Trypanosoma cruzi recombinant antigens (JL8, MAP, and TcPo). High sensitivity (99.4%) and specificity (99.3%) were obtained when JL8 was combined with MAP (JM) and tested with 150 serum samples from chagasic and 142 nonchagasic individuals. Moreover, JM also diagnosed 84.2% of patients in the acute phase of T. cruzi infection. PMID:14715803

  7. Moléstia de chagas crônica associada a leucemia linfática: ocorrência de encefalite aguda como alteração do estado imunitário Chronic Chagas disease associated with lymphatic leukemia: occurrence of acute encephalitis as a possible alteration of the immune state

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    L. C. Mattosinhi França

    1969-03-01

    Full Text Available É relatado um caso de paciente apresentando a forma crônica da doença de Chagas, no qual foi observada a presença de encefalite chagásica aguda, com demonstração de leishmanias no sistema nervoso central. O caso é único na literatura, sendo interpretado como devido a agravamento da forma crônica da doença de Chagas pela presença de leucemia linfática crônica associada. A existência de leucemia linfática pode levar à extinção de clones linfocitários responsáveis por fenômenos imunitários, criando, assim, condições para o agravamento e agudização da forma crônica da doença de Chagas.A case of chronic Chagas disease, associated with chronic lymphocitic leukemia is reported. Acute manifestations of Chagas disease, characterized by acute encephalitis, with demonstration of Leishmaniae in the central nervous system were observed. This aspect is unique in the literature, since Chagas encephalitis appears only as a manifestation of the acute form of the disease, and not as a complication of the chronic form. The fact is interpreted, in this case, as secondary to alteration of the immune state, due to the presence of chronic lymphocitic leukemia.

  8. Transmissão da doença de Chagas por transplante renal: ocorrência da forma aguda da doença em dois receptores de um mesmo doador Transmission of Chagas' disease through transplantede kidney: occurrence of the acute form of the disease in two recipients from the same donor

    Directory of Open Access Journals (Sweden)

    A.S. Ferraz

    1993-10-01

    Full Text Available São apresentados dois casos de doença de Chagas aguda, adquiridos através de transplante de rins originários de um mesmo doador. O presente relato confirma a transmissão da doença de Chagas a partir do transplante renal e reforça a necessidade de exclusão de doadores renais infectados pelo Trypanosoma cruzi.Two cases of acute Chagas' disease acquired after renal transplantation are reported. The two patients received the kidney from the same donor. The present paper confirms this form of transmission of Chagas' disease and reinforces the need to exclude kidney donors with Trypanosoma cruzi infection.

  9. Trypanosoma cruzi genotyping supports a common source of infection in a school-related oral outbreak of acute Chagas disease in Venezuela.

    Science.gov (United States)

    Díaz-Bello, Z; Thomas, M C; López, M C; Zavala-Jaspe, R; Noya, O; DE Noya, B Alarcón; Abate, T

    2014-01-01

    Trypanosoma cruzi I, a discrete typing unit (DTU) found in human infections in Venezuela and other countries of the northern region of South America and in Central America, has been recently classified into five intra-DTU genotypes (Ia, Ib, Ic, Id, Ie) based on sequence polymorphisms found in the spliced leader intergenic region. In this paper we report the genotype identification of T. cruzi human isolates from one outbreak of acute orally acquired Chagas disease that occurred in a non-endemic region of Venezuela and from T. cruzi triatomine and rat isolates captured at a guava juice preparation site which was identified as the presumptive source of infection. The genotyping of all these isolates as TcId supports the view of a common source of infection in this oral Chagas disease outbreak through the ingestion of guava juice. Implications for clinical manifestations and dynamics of transmission cycles are discussed.

  10. Extraction of Trypanosoma cruzi DNA from food: a contribution to the elucidation of acute Chagas disease outbreaks.

    Science.gov (United States)

    Ferreira, Renata Trotta Barroso; Melandre, Aline Martins; Cabral, Maria Luiza; Branquinho, Maria Regina; Cardarelli-Leite, Paola

    2016-04-01

    Before 2004, the occurrence of acute Chagas disease (ACD) by oral transmission associated with food was scarcely known or investigated. Originally sporadic and circumstantial, ACD occurrences have now become frequent in the Amazon region, with recently related outbreaks spreading to several Brazilian states. These cases are associated with the consumption of açai juice by waste reservoir animals or insect vectors infected with Trypanosoma cruzi in endemic areas. Although guidelines for processing the fruit to minimize contamination through microorganisms and parasites exist, açai-based products must be assessed for quality, for which the demand for appropriate methodologies must be met. Dilutions ranging from 5 to 1,000 T. cruzi CL Brener cells were mixed with 2mL of acai juice. Four Extraction of T. cruzi DNA methods were used on the fruit, and the cetyltrimethyl ammonium bromide (CTAB) method was selected according to JRC, 2005. DNA extraction by the CTAB method yielded satisfactory results with regard to purity and concentration for use in PCR. Overall, the methods employed proved that not only extraction efficiency but also high sensitivity in amplification was important. The method for T. cruzi detection in food is a powerful tool in the epidemiological investigation of outbreaks as it turns epidemiological evidence into supporting data that serve to confirm T. cruzi infection in the foods. It also facilitates food quality control and assessment of good manufacturing practices involving acai-based products.

  11. Early molecular diagnosis of acute Chagas disease after transplantation with organs from Trypanosoma cruzi-infected donors.

    Science.gov (United States)

    Cura, C I; Lattes, R; Nagel, C; Gimenez, M J; Blanes, M; Calabuig, E; Iranzo, A; Barcan, L A; Anders, M; Schijman, A G

    2013-12-01

    Organ transplantation (TX) is a novel transmission modality of Chagas disease. The results of molecular diagnosis and characterization of Trypanosoma cruzi acute infection in naïve TX recipients transplanted with organs from infected deceased donors are reported. Peripheral blood and cerebrospinal fluid samples from the TX recipients of organs from infected donors were prospectively and sequentially studied for detection of T. cruzi by means of kinetoplastid DNA polymerase chain reaction (kDNA-PCR). In positive blood samples, a PCR algorithm for identification of T. cruzi Discrete Typing Units (DTUs) and quantitative real-time PCR (qPCR) to quantify parasitic loads were performed. Minicircle signatures of T. cruzi infecting populations were also analyzed using restriction fragment length polymorphism (RFLP)-PCR. Eight seronegative TX recipients from four infected donors were studied. In five, the infection was detected at 68.4 days post-TX (36-98 days). In one case, it was transmitted to two of three TX recipients. The comparison of the minicircle signatures revealed nearly identical RFLP-PCR profiles, confirming a common source of infection. The five cases were infected by DTU TcV. This report reveals the relevance of systematic monitoring of TX recipients using PCR strategies in order to provide an early diagnosis allowing timely anti-trypanosomal treatment. © Copyright 2013 The American Society of Transplantation and the American Society of Transplant Surgeons.

  12. Extraction of Trypanosoma cruzi DNA from food: a contribution to the elucidation of acute Chagas disease outbreaks

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    Renata Trotta Barroso Ferreira

    2016-04-01

    Full Text Available Abstract: INTRODUCTION: Before 2004, the occurrence of acute Chagas disease (ACD by oral transmission associated with food was scarcely known or investigated. Originally sporadic and circumstantial, ACD occurrences have now become frequent in the Amazon region, with recently related outbreaks spreading to several Brazilian states. These cases are associated with the consumption of açai juice by waste reservoir animals or insect vectors infected with Trypanosoma cruzi in endemic areas. Although guidelines for processing the fruit to minimize contamination through microorganisms and parasites exist, açai-based products must be assessed for quality, for which the demand for appropriate methodologies must be met. METHODS: Dilutions ranging from 5 to 1,000 T. cruzi CL Brener cells were mixed with 2mL of acai juice. Four Extraction of T. cruzi DNA methods were used on the fruit, and the cetyltrimethyl ammonium bromide (CTAB method was selected according to JRC, 2005. RESULTS: DNA extraction by the CTAB method yielded satisfactory results with regard to purity and concentration for use in PCR. Overall, the methods employed proved that not only extraction efficiency but also high sensitivity in amplification was important. CONCLUSIONS: The method for T. cruzi detection in food is a powerful tool in the epidemiological investigation of outbreaks as it turns epidemiological evidence into supporting data that serve to confirm T. cruzi infection in the foods. It also facilitates food quality control and assessment of good manufacturing practices involving acai-based products.

  13. Clinical findings and prognosis of patients hospitalized for acute decompensated heart failure: Analysis of the influence of Chagas etiology and ventricular function

    Science.gov (United States)

    Moreira, Henry Fukuda; Ayub-Ferreira, Silvia Moreira; Conceição-Souza, Germano Emilio; Salemi, Vera Maria Cury; Chizzola, Paulo Roberto; Oliveira, Mucio Tavares; Lage, Silvia Helena Gelas; Bocchi, Edimar Alcides; Issa, Victor Sarli

    2018-01-01

    Aims Explore the association between clinical findings and prognosis in patients with acute decompensated heart failure (ADHF) and analyze the influence of etiology on clinical presentation and prognosis. Methods and results Prospective cohort of 500 patients admitted with ADHF from Aug/2013-Feb/2016; patients were predominantly male (61.8%), median age was 58 (IQ25-75% 47–66 years); etiology was dilated cardiomyopathy in 141 (28.2%), ischemic heart disease in 137 (27.4%), and Chagas heart disease in 113 (22.6%). Patients who died (154 [30.8%]) or underwent heart transplantation (53[10.6%]) were younger (56 years [IQ25-75% 45–64 vs 60 years, IQ25-75% 49–67], P = 0.032), more frequently admitted for cardiogenic shock (20.3% vs 6.8%, Pheart transplant was higher among patients with Chagas (50.5%). Conclusions A physical exam may identify patients at higher risk in a contemporaneous population. Our findings support specific therapies targeted at Chagas patients in the setting of ADHF. PMID:29432453

  14. Pathogenesis of acute experimental liver amebiasis.

    Science.gov (United States)

    Pérez-Tamayo, Ruy; Montfort, Irmgard; García, Alfonso Olivos; Ramos, Espiridión; Ostria, Carlos Barba

    2006-02-01

    Classical descriptions of the pathology of amebiasis portray the parasite as the cause of tissue damage and destruction, and in recent years a number of amebic molecules have been identified as virulence factors. In this review we describe a series of experiments that suggest a more complex host-parasite relation, at least during the early stages of acute experimental amebic liver abscess in hamsters. The problems of extrapolating experiments in vitro to explain observations in vivo are discussed. The role of amebic cysteine proteases is examined and evidence presented to suggest that they are primarily related not to tissue damage but to amebic survival, which is required for the progression of the lesion. Inflammation is shown to be not only the major cause of tissue damage but also an absolute requirement for amebic survival in the liver, whereas complement and ischemia are not involved in the disappearance of the parasite in the absence of inflammation.

  15. Heterologous Infection During Chagas' Disease

    Science.gov (United States)

    Sibona, G. J.; Condat, C. A.; Cossi Isasi, S.

    2007-05-01

    Human populations are often infected with more than one parasite strain. This is frequently the case with ChagasŠ disease, which is endemic to large regions of Latin America. In the present work we study the dynamics of the heterologous infection for this disease, using a model for the interaction between the trypanosoma cruzi parasite and the immune system. We find the dependence of the nature of the post-acute stage on the parameters characterizing the inoculated infectious strains.

  16. Tympanic membrane changes in experimental acute otitis media and myringotomy

    DEFF Research Database (Denmark)

    Alzbutiene, G.; Hermansson, A.; Caye-Thomasen, P.

    2008-01-01

    OBJECTIVE: The present experimental study explored pathomorphological changes and calcium depositions in the tympanic membrane during experimental acute otitis media caused by nontypeable Haemophilus influenzae in myringotomized and nonmyringotomized ears. MATERIAL AND METHODS: A rat model of exp...

  17. On an acute case of Chagas disease in a region under vector control in the state of São Paulo, Brazil Sobre caso de doença de Chagas aguda em região de vetores controlados no Estado de São Paulo, Brasil

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    Dalva M.V. Wanderley

    2010-06-01

    Full Text Available No vector transmitted cases of Chagas disease had been notified in the state of São Paulo since the 1970s. However, in March, 2006, the death of a six-year-old boy from the municipality of Itaporanga was notified to the Center for Epidemiological Survey of the São Paulo State Health Secretariat: an autochthonous case of acute Chagas disease. The postmortem histopathological examination performed in the Hospital das Clínicas of the Botucatu School of Medicine confirmed the diagnosis. Reference to hospital records, consultation with the health professionals involved in the case and interviews with members of the patient's family supplied the basis for this study. We investigated parasite route of transmission, probable local reservoirs and vectors. No further human cases of acute Chagas disease were diagnosed. No locally captured vectors or reservoirs were found infected with Trypanosoma cruzi. Alternative transmission hypotheses - such as the possible ingestion of foods contaminated with vector excreta - are discussed, as well as the need to keep previously endemic regions and infested houses under close surveillance. Clinicians should give due attention to such signs as uni- or bilateral palpebral edema, cardiac failure, myocarditis, pericarditis, anasarca and atypical signs of nephrotic syndrome or nephritis and consider the diagnostic hypothesis of Chagas disease.Desde a década de 1970 não se notificavam casos autóctones de doença de Chagas aguda em São Paulo. Em março de 2006 a Vigilância Epidemiológica registrou óbito por doença de Chagas aguda, em Itaporanga, de paciente de seis anos de idade. Exame histopatológico post mortem realizado no Hospital das Clínicas da Faculdade de Medicina de Botucatu confirmou o diagnóstico. Consultamos prontuários de hospitais e entrevistamos profissionais de saúde envolvidos além de familiares do paciente. Descrevemos medidas adotadas in loco para identificar a via de transmiss

  18. Série de casos agudos de doença de Chagas atendidos num serviço terciário de Manaus, Estado do Amazonas, de 1980 a 2006 Series of acute Chagas' disease cases attended at a tertiary-level clinic in Manaus, State of Amazonas, from 1980 to 2006

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    Wuelton Marcelo Monteiro

    2010-04-01

    Full Text Available INTRODUÇÃO: A doença de Chagas é um problema emergente e negligenciado na Região Amazônica. MÉTODOS: Descreve-se uma série de casos agudos autóctones de doença de Chagas atendidos na Fundação de Medicina Tropical do Amazonas, Manaus, de 1980 a 2006. RESULTADOS: Registraram-se 29 casos, sendo 19 do sexo masculino e 10 casos do sexo feminino. Quinze eram casos isolados e 14 provenientes de surtos. Os sinais/sintomas mais freqüentes foram febre, fadiga, cefaléia, mialgia, calafrios, palidez, dispnéia e edema de face e de membros inferiores. Não foi registrado nenhum óbito. CONCLUSÕES: A doença incidiu com frequência em jovens. Os métodos parasitológicos mostraram elevada sensibilidade.INTRODUCTION: Chagas disease is an emerging and neglected problem in the Brazilian Amazon region. METHODS: This study describes a series of acute autochthonous cases of Chagas disease that were attended at the Tropical Medicine Foundation of Amazonas, Manaus, between 1980 and 2006. RESULTS: Twenty-nine cases were recorded: 19 (65.5% were male and 10 (34.5% cases were female. Fifteen (51.7% were isolated cases and 14 (48.3% were from outbreaks. The commonest signs and symptoms were fever, fatigue, headache, myalgia, chills, pallor, dyspnea and edema of the face and lower limbs. No deaths were recorded. CONCLUSIONS: The disease occurred frequently among young people. The parasitological methods showed high sensitivity.

  19. Augmentation of suppressed antibody responses in mice during experimental Chagas' disease by T helper cells activated in a time-dependent mode of immunization.

    Science.gov (United States)

    Choromanski, L; Kuhn, R E

    1990-01-01

    Mice infected with the protozoan parasite Trypanosoma cruzi, the causative agent of human Chagas' disease, develop immunosuppressed responses to heterologous antigens. Experiments were performed using infected mice in the acute stage of infection to assess immunoregulatory activities during induction of direct plaque-forming cells (DPFC) to sheep erythrocytes (SRBC), hapten-conjugated SRBC (TNP-SRBC), and horse erythrocytes (TNP-HRBC). Studies in vivo demonstrated that anti-SRBC responses were best enhanced when T. cruzi-infected mice were injected with primed T cells derived from normal or infected mice immunized four days previously. The presence of enhancing capacities for DPFC responses by T cells from T. cruzi-infected mice were also supported by experiments examining the hapten-carrier effect. Preimmunization of infected mice with SRBC or HRBC four days before injection of hapten-homologous (TNP-SRBC or TNP-HRBC) carrier resulted in markedly augmented anti-hapten antibody responses. These results show that functional help provided by T cells activated during priming and exposed to a challenge dose of antigen (SRBC) in a time-dependent mode can overcome the effect of immunosuppression in T. cruzi-infected mice.

  20. Metabolic acidosis aggravates experimental acute kidney injury.

    Science.gov (United States)

    Magalhães, Patrícia Andréa da Fonseca; de Brito, Teresinha Silva; Freire, Rosemayre Souza; da Silva, Moisés Tolentino Bento; dos Santos, Armênio Aguiar; Vale, Mariana Lima; de Menezes, Dalgimar Beserra; Martins, Alice Maria Costa; Libório, Alexandre Braga

    2016-02-01

    Ischemia/reperfusion (I/R) injury and metabolic acidosis (MA) are two critical conditions that may simultaneously occur in clinical practice. The result of this combination can be harmful to the kidneys, but this issue has not been thoroughly investigated. The present study evaluated the influence of low systemic pH on various parameters of kidney function in rats that were subjected to an experimental model of renal I/R injury. Metabolic acidosis was induced in male Wistar rats by ingesting ammonium chloride (NH4Cl) in tap water, beginning 2 days before ischemic insult and maintained during the entire study. Ischemia/reperfusion was induced by clamping both renal arteries for 45 min, followed by 48 h of reperfusion. Four groups were studied: control (subjected to sham surgery, n=8), I/R (n=8), metabolic acidosis (MA; 0.28 M NH4Cl solution and sham surgery, n=6), and MA+I/R (0.28 M NH4Cl solution plus I/R, n=9). Compared with I/R rats, MA+I/R rats exhibited higher mortality (50 vs. 11%, p=0.03), significant reductions of blood pH, plasma bicarbonate (pBic), and standard base excess (SBE), with a severe decline in the glomerular filtration rate and tubular function. Microscopic tubular injury signals were detected. Immunofluorescence revealed that the combination of MA and I/R markedly increased nuclear factor κB (NF-κB) and heme-oxygenase 1 (HO-1), but it did not interfere with the decrease in endothelial nitric oxide synthase (eNOS) expression that was caused by I/R injury. Acute ischemic kidney injury is exacerbated by acidic conditions. Copyright © 2016 Elsevier Inc. All rights reserved.

  1. Studies in search of a suitable experimental insect model for xenodiagnosis of hosts with Chagas' disease: 2 - Attempts to upgrade the reliability and the efficacy of xenodiagnosis in chronic Chagas' disease Estudos em busca de um inseto modelo experimental para xenodiagnóstico em hospedeiros com doença de Chagas: 2. Tentativas para aumentar a credibilidade e a eficiência do xenodiagnóstico na doença de Chagas crônica

    Directory of Open Access Journals (Sweden)

    Alina Perlowagora Szumlewicz

    1987-06-01

    Full Text Available In order to upgrade the reliability of xenodiagnosis, attention has been directed towards population dynamics of the parasite, with particular interest for the following factors: 1. Parasite density which by itself is not a research objective, but by giving an accurate portrayal of parasite development and multiplication, has been incorporated in screening of bugs for xenodiagnosis. 2. On the assumption that food availability might increase parasite density, bugs from xenodiagnosis have been refed at biweekly intervals on chicken blood. 3. Infectivity rates and positives harbouring large parasite yields were based on gut infections, in which the parasite population comprised of all developmental forms was more abundant and easier to detect than in fecal infections, thus minimizing the probability of recording false negatives. 4. Since parasite density, low in the first 15 days of infection, increases rapidly in the following 30 days, the interval of 45 days has been adopted for routine examination of bugs from xenodiagnosis. By following the enumerated measures, all aiming to reduce false negative cases, we are getting closer to a reliable xenodiagnostic procedure. Upgrading the efficacy of xenodiagnosis is also dependent on the xenodiagnostic agent. Of 9 investigated vector species, Panstrongylus megistus deserves top priority as a xenodiagnostic agent. Its extraordinary capability to support fast development and vigorous multiplication of the few parasites, ingested from the host with chronic Chagas' disease, has been revealed by the strikingly close infectivity rates of 91.2% vs. 96.4% among bugs engorged from the same host in the chronic and acute phase of the disease respectively (Table V, the latter comporting an estimated number of 12.3 x 10[raised to the power of 3] parasites in the circulation at the time of xenodiagnosis, as reported previously by the authors (1982.Assumindo que a otimização do xenodiagnóstico poderia apresentar um

  2. Mast Cell Coupling to the Kallikrein–Kinin System Fuels Intracardiac Parasitism and Worsens Heart Pathology in Experimental Chagas Disease

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    Clarissa R. Nascimento

    2017-08-01

    Full Text Available During the course of Chagas disease, infectious forms of Trypanosoma cruzi are occasionally liberated from parasitized heart cells. Studies performed with tissue culture trypomastigotes (TCTs, Dm28c strain demonstrated that these parasites evoke neutrophil/CXCR2-dependent microvascular leakage by activating innate sentinel cells via toll-like receptor 2 (TLR2. Upon plasma extravasation, proteolytically derived kinins and C5a stimulate immunoprotective Th1 responses via cross-talk between bradykinin B2 receptors (B2Rs and C5aR. Awareness that TCTs invade cardiovascular cells in vitro via interdependent activation of B2R and endothelin receptors [endothelin A receptor (ETAR/endothelin B receptor (ETBR] led us to hypothesize that T. cruzi might reciprocally benefit from the formation of infection-associated edema via activation of kallikrein–kinin system (KKS. Using intravital microscopy, here we first examined the functional interplay between mast cells (MCs and the KKS by topically exposing the hamster cheek pouch (HCP tissues to dextran sulfate (DXS, a potent “contact” activator of the KKS. Surprisingly, although DXS was inert for at least 30 min, a subtle MC-driven leakage resulted in factor XII (FXII-dependent activation of the KKS, which then amplified inflammation via generation of bradykinin (BK. Guided by this mechanistic insight, we next exposed TCTs to “leaky” HCP—forged by low dose histamine application—and found that the proinflammatory phenotype of TCTs was boosted by BK generated via the MC/KKS pathway. Measurements of footpad edema in MC-deficient mice linked TCT-evoked inflammation to MC degranulation (upstream and FXII-mediated generation of BK (downstream. We then inoculated TCTs intracardiacally in mice and found a striking decrease of parasite DNA (quantitative polymerase chain reaction; 3 d.p.i. in the heart of MC-deficient mutant mice. Moreover, the intracardiac parasite load was significantly reduced in WT

  3. Immunosuppression and Chagas disease: a management challenge.

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    María-Jesús Pinazo

    Full Text Available Immunosuppression, which has become an increasingly relevant clinical condition in the last 50 years, modifies the natural history of Trypanosoma cruzi infection in most patients with Chagas disease. The main goal in this setting is to prevent the consequences of reactivation of T. cruzi infection by close monitoring. We analyze the relationship between Chagas disease and three immunosuppressant conditions, including a description of clinical cases seen at our center, a brief review of the literature, and recommendations for the management of these patients based on our experience and on the data in the literature. T. cruzi infection is considered an opportunistic parasitic infection indicative of AIDS, and clinical manifestations of reactivation are more severe than in acute Chagas disease. Parasitemia is the most important defining feature of reactivation. Treatment with benznidazole and/or nifurtimox is strongly recommended in such cases. It seems reasonable to administer trypanocidal treatment only to asymptomatic immunosuppressed patients with detectable parasitemia, and/or patients with clinically defined reactivation. Specific treatment for Chagas disease does not appear to be related to a higher incidence of neoplasms, and a direct role of T. cruzi in the etiology of neoplastic disease has not been confirmed. Systemic immunosuppressive diseases or immunosuppressants can modify the natural course of T. cruzi infection. Immunosuppressive doses of corticosteroids have not been associated with higher rates of reactivation of Chagas disease. Despite a lack of evidence-based data, treatment with benznidazole or nifurtimox should be initiated before immunosuppression where possible to reduce the risk of reactivation. Timely antiparasitic treatment with benznidazole and nifurtimox (or with posaconazole in cases of therapeutic failure has proven to be highly effective in preventing Chagas disease reactivation, even if such treatment has not been

  4. Immunosuppression and Chagas disease: a management challenge.

    Science.gov (United States)

    Pinazo, María-Jesús; Espinosa, Gerard; Cortes-Lletget, Cristina; Posada, Elizabeth de Jesús; Aldasoro, Edelweiss; Oliveira, Inés; Muñoz, Jose; Gállego, Montserrat; Gascon, Joaquim

    2013-01-01

    Immunosuppression, which has become an increasingly relevant clinical condition in the last 50 years, modifies the natural history of Trypanosoma cruzi infection in most patients with Chagas disease. The main goal in this setting is to prevent the consequences of reactivation of T. cruzi infection by close monitoring. We analyze the relationship between Chagas disease and three immunosuppressant conditions, including a description of clinical cases seen at our center, a brief review of the literature, and recommendations for the management of these patients based on our experience and on the data in the literature. T. cruzi infection is considered an opportunistic parasitic infection indicative of AIDS, and clinical manifestations of reactivation are more severe than in acute Chagas disease. Parasitemia is the most important defining feature of reactivation. Treatment with benznidazole and/or nifurtimox is strongly recommended in such cases. It seems reasonable to administer trypanocidal treatment only to asymptomatic immunosuppressed patients with detectable parasitemia, and/or patients with clinically defined reactivation. Specific treatment for Chagas disease does not appear to be related to a higher incidence of neoplasms, and a direct role of T. cruzi in the etiology of neoplastic disease has not been confirmed. Systemic immunosuppressive diseases or immunosuppressants can modify the natural course of T. cruzi infection. Immunosuppressive doses of corticosteroids have not been associated with higher rates of reactivation of Chagas disease. Despite a lack of evidence-based data, treatment with benznidazole or nifurtimox should be initiated before immunosuppression where possible to reduce the risk of reactivation. Timely antiparasitic treatment with benznidazole and nifurtimox (or with posaconazole in cases of therapeutic failure) has proven to be highly effective in preventing Chagas disease reactivation, even if such treatment has not been formally

  5. Ecological scenario and Trypanosoma cruzi DTU characterization of a fatal acute Chagas disease case transmitted orally (Espírito Santo state, Brazil).

    Science.gov (United States)

    Dario, Maria Augusta; Rodrigues, Marina Silva; Barros, Juliana Helena da Silva; Xavier, Samanta Cristina das Chagas; D'Andrea, Paulo Sérgio; Roque, André Luiz Rodrigues; Jansen, Ana Maria

    2016-08-31

    Trypanosoma cruzi infection via oral route results in outbreaks or cases of acute Chagas disease (ACD) in different Brazilian regions and poses a novel epidemiological scenario. In the Espírito Santo state (southeastern Brazil), a fatal case of a patient with ACD led us to investigate the enzootic scenario to avoid the development of new cases. At the studied locality, Triatoma vitticeps exhibited high T. cruzi infection rates and frequently invaded residences. Sylvatic and domestic mammals in the Rio da Prata locality, where the ACD case occurred, and in four surrounding areas (Baia Nova, Buenos Aires, Santa Rita and Todos os Santos) were examined and underwent parasitological and serological tests. Triatomines were collected for a fecal material exam, culturing and mini-exon gene molecular characterization, followed by RFLP-PCR of H3/Alul. Paraffin-embedded cardiac tissue of a patient was washed with xylene to remove paraffin and DNA was extracted using the phenol-chloroform method. For genotype characterization, PCR was performed to amplify the 1f8, GPI and 18S rRNA genes. In the case of V7V8 SSU rRNA, the PCR products were molecularly cloned. PCR products were sequenced and compared to sequences in GenBank. Phylogenetic analysis using maximum likelihood method with 1000 bootstrap replicates was performed. None of the animals showed positive hemocultures. Three rodents and two dogs showed signs of infection, as inferred from borderline serological titers. T. vitticeps was the only triatomine species identified and showed T. cruzi infection by DTUs TcI and TcIV. The analysis of cardiac tissue DNA showed mixed infection by T. cruzi (DTUs I, II, III and IV) and Trypanosoma dionisii. Each case or outbreak of ACD should be analyzed as a particular epidemiological occurrence. The results indicated that mixed infections in humans may play a role in pathogenicity and may be more common than is currently recognized. Direct molecular characterization from biological

  6. Pediatric clinical pharmacology studies in Chagas disease: focus on Argentina.

    Science.gov (United States)

    Garcia-Bournissen, Facundo; Altcheh, Jaime; Giglio, Norberto; Mastrantonio, Guido; Della Védova, Carlos Omar; Koren, Gideon

    2009-01-01

    Chagas disease is a neglected parasitic disease endemic in the Americas. It mainly affects impoverished populations and the acute phase of the infection mostly affects children. Many cases have also been detected in nonendemic countries as a result of recent migratory trends. The chronic phase is relatively asymptomatic, but 30% of patients with chronic infection eventually develop cardiac and digestive complications that commonly lead to death or disability. Only two drugs are available for the treatment of Chagas disease, benznidazole and nifurtimox. These drugs have been shown to be effective in the treatment of both acute and early chronic phases in children, but the pharmacokinetics of these drugs have never been studied in this population. We have set out to conduct a pharmacokinetics study of benznidazole in a pediatric population with Chagas disease. The results of this study are expected to allow better estimation of the optimal doses and schedule of pharmacotherapy for Chagas disease in children.

  7. Treatment of acute experimental schistosomiasis Tratamento da esquistossomose aguda experimental

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    Zilton A. Andrade

    1989-12-01

    Full Text Available A model of acute schistosomiasis of the mouse was used to observe whether curative treatment would be followed by an enhancement of the hepatic and splenic lesions, as a consequence of the massive destruction of worms and eggs within the portal system. Mice infected with 50 cercariae of Schistosoma mansoni were treated with both oxamniquine and praziquantel on the 50th day of infection and submitted to a sequential histologic examination from the 2nd to the 45th day after treatment. Although severe focal lesions due to dead and disintegranting worms were present in the livers of the treated animals, no aggravation of the general changes (reative hepatitis and splenitis, or periovular granulomas was seen in comparison with a control non-treated group. Of 50 animals treated during the acute phase of schistosomiasis only one died espontaneously, while 16 ou of 30 infected controls died before the end of the experiment. The present investigation indicates that curative treatment during the acute phase of schistosomiasis does not enhance previous lesions at first and results in progressive disappearance of the lesions starting six days following chemotherapy.Foi utilizado um modelo de esquistossomose aguda do camundongo para testar se o tratamentop curativo da parasitose nesta fase poderia produzir uma exacerbação das lesões hepáticas e esplênicas, em virtude da destruição maciça de vermes e ovos nointerior do sistema porta. Camundongos infectados com 50 cercárias do Schistosoma mansoni foram tratados no 50º dia da infecção por uma combinação de oxamniquine e praziquantel e submetidos a exames histopatológicos seqüenciados desde o 2º até o 45º dia após o tratamento. Muito embora tenham sido encontrados lesões focais intensas causadas por vermes mortos no interior do fígado, não foi encontrada qualquer evidência de agravamento das lesões gerais (hepatite reacional e esplenite, ou nos granulomas periovulares quando se fez

  8. Chagas disease in prehistory

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    Luiz F. Ferreira

    Full Text Available The classical hypothesis proposes that Chagas disease has been originated in the Andean region among prehistoric people when they started domesticating animals, changing to sedentary habits, and adopting agriculture. These changes in their way of life happened nearly 6,000 years ago. However, paleoparasitological data based on molecular tools showed that Trypanosoma cruzi infection and Chagas disease were commonly found both in South and North American prehistoric populations long before that time, suggesting that Chagas disease may be as old as the human presence in the American continent. The study of the origin and dispersion of Trypanosoma cruzi infection among prehistoric human populations may help in the comprehension of the clinical and epidemiological questions on Chagas disease that still remain unanswered.

  9. Dobutamine Stress Echocardiography Safety in Chagas Disease Patients

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    Daniela do Carmo Rassi

    Full Text Available Abstract Background: A few decades ago, patients with Chagas disease were predominantly rural workers, with a low risk profile for obstructive coronary artery disease (CAD. As urbanization has increased, they became exposed to the same risk factors for CAD of uninfected individuals. Dobutamine stress echocardiography (DSE has proven to be an important tool in CAD diagnosis. Despite being a potentially arrhythmogenic method, it is safe for coronary patients without Chagas disease. For Chagas disease patients, however, the indication of DSE in clinical practice is uncertain, because of the arrhythmogenic potential of that heart disease. Objectives: To assess DSE safety in Chagas disease patients with clinical suspicion of CAD, as well as the incidence of arrhythmias and adverse events during the exam. Methods: Retrospective analysis of a database of patients referred for DSE from May/2012 to February/2015. This study assessed 205 consecutive patients with Chagas disease suspected of having CAD. All of them had their serology for Chagas disease confirmed. Results: Their mean age was 64±10 years and most patients were females (65.4%. No patient had significant adverse events, such as acute myocardial infarction, ventricular fibrillation, asystole, stroke, cardiac rupture and death. Regarding arrhythmias, ventricular extrasystoles occurred in 48% of patients, and non-sustained ventricular tachycardia in 7.3%. Conclusion: DSE proved to be safe in this population of Chagas disease patients, in which no potentially life-threatening outcome was found.

  10. Chagas disease in the Amazon Region

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    Hugo Marcelo Aguilar

    2007-10-01

    Full Text Available The risk that Chagas disease becomes established as a major endemic threat in Amazonia (the world's largest tropical biome, today inhabited by over 30 million people relates to a complex set of interacting biological and social determinants. These include intense immigration from endemic areas (possibly introducing parasites and vectors, extensive landscape transformation with uncontrolled deforestation, and the great diversity of wild Trypanosoma cruzi reservoir hosts and vectors (25 species in nine genera, which maintain intense sylvatic transmission cycles. Invasion of houses by adventitious vectors (with infection rates > 60% is common, and focal adaptation of native triatomines to artificial structures has been reported. Both acute (~ 500 and chronic cases of autochthonous human Chagas disease have been documented beyond doubt in the region. Continuous, low-intensity transmission seems to occur throughout the Amazon, and generates a hypoendemic pattern with seropositivity rates of ~ 1-3%. Discrete foci also exist in which transmission is more intense (e.g., in localized outbreaks probably linked to oral transmission and prevalence rates higher. Early detection-treatment of acute cases is crucial for avoiding further dispersion of endemic transmission of Chagas disease in Amazonia, and will require the involvement of malaria control and primary health care systems. Comprehensive eco-epidemiological research, including prevalence surveys or the characterization of transmission dynamics in different ecological settings, is still needed. The International Initiative for Chagas Disesae Surveillance and Prevention in the Amazon provides the framework for building up the political and scientific cooperation networks required to confront the challenge of preventing Chagas disease in Amazonia.

  11. Chagas disease in the Amazon Region

    Directory of Open Access Journals (Sweden)

    Hugo Marcelo Aguilar

    Full Text Available The risk that Chagas disease becomes established as a major endemic threat in Amazonia (the world's largest tropical biome, today inhabited by over 30 million people relates to a complex set of interacting biological and social determinants. These include intense immigration from endemic areas (possibly introducing parasites and vectors, extensive landscape transformation with uncontrolled deforestation, and the great diversity of wild Trypanosoma cruzi reservoir hosts and vectors (25 species in nine genera, which maintain intense sylvatic transmission cycles. Invasion of houses by adventitious vectors (with infection rates > 60% is common, and focal adaptation of native triatomines to artificial structures has been reported. Both acute (~ 500 and chronic cases of autochthonous human Chagas disease have been documented beyond doubt in the region. Continuous, low-intensity transmission seems to occur throughout the Amazon, and generates a hypoendemic pattern with seropositivity rates of ~ 1-3%. Discrete foci also exist in which transmission is more intense (e.g., in localized outbreaks probably linked to oral transmission and prevalence rates higher. Early detection-treatment of acute cases is crucial for avoiding further dispersion of endemic transmission of Chagas disease in Amazonia, and will require the involvement of malaria control and primary health care systems. Comprehensive eco-epidemiological research, including prevalence surveys or the characterization of transmission dynamics in different ecological settings, is still needed. The International Initiative for Chagas Disesae Surveillance and Prevention in the Amazon provides the framework for building up the political and scientific cooperation networks required to confront the challenge of preventing Chagas disease in Amazonia.

  12. [Diagnosis and treatment of Chagas disease].

    Science.gov (United States)

    Murcia, Laura; Carrilero, Bartolomé; Saura, Daniel; Iborra, M Asunción; Segovia, Manuel

    2013-02-01

    Trypanosoma cruzi infection, or Chagas disease, was discovered more than 100 years ago by Carlos Chagas. Although the infection kills more than 15,000 people each year, it is still classified as a neglected tropical disease. Today, this disease affects eight million people in 21 Latin American countries and, due to immigration, is also present in non-endemic countries. In recent years, the size of the immigrant population with chronic imported forms of Chagas disease has increased in Spain. In addition, several cases of congenital transmission have been reported. Some patients have severe infection and require specialized treatment such as pacemaker implantation or even heart transplantation, representing a considerable clinical, social and economic burden, particularly in areas with a large immigrant population. Since the 1960s, the only drugs available for the etiological treatment of this infection have been benznidazole and nifurtimox. Although new, more effective and better tolerated compounds are urgently needed, treatment with these trypanocidal drugs is recommended in both the acute and chronic stages of Chagas disease. New strategies for diagnosis and infection control in chronically infected patients have recently been reported, allowing the effectiveness of treatments to be assessed. Copyright © 2013 Elsevier España, S.L. All rights reserved.

  13. Oral transmission of Chagas disease: importance of Trypanosoma cruzi biodeme in the intragastric experimental infection Transmissão oral da doença de Chagas: importância do biodema do Trypanosoma cruzi na infecção experimental intragástrica

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    Edson Luiz P. CAMANDAROBA

    2002-04-01

    Full Text Available Oral transmission of Trypanosoma cruzi has been suspected when epidemic episodes of acute infection were observed in areas devoid of domiciled insect vectors. Considering that the distribution of T. cruzi biodemes differs in sylvatic and domestic cycles, results of studies on biodemes can be of interest regarding oral transmission. The infectivity of T. cruzi strains of different biodemes was tested in mice subjected to infection by the digestive route (gavage. Swiss mice were infected either with the Peruvian strain (Biodeme Type I, Z2b or the Colombian strain (Biodeme Type III, Z1, or T. cruzi I; for control, intraperitoneal inoculation was performed in a group of mice. The Colombian strain revealed a similar high infectivity and pathogenicity when either route of infection was used. However, the Peruvian strain showed contrasting levels of infectivity and pathogenicity, being high by intraperitoneal inoculation and low when the gastric route was used. The higher infectivity of the Colombian strain (Biodeme Type III by gastric inoculation is in keeping with its role in the epidemic episodes of acute Chagas disease registered in the literature, since strains belonging to Biodeme III are most often found in sylvatic hosts.A ocorrência de microepidemias de infecção pelo Trypanosoma cruzi atribuidas à ingestão de alimentos contaminados com excreta de vetores ou de reservatórios vertebrados, em áreas rurais chamou a atenção para este tipo não vetorial de transmissão da doença de Chagas. Considerando que cepas de diferentes biodemas se distribuem diferentemente nos ciclos silvestre e domiciliar de transmissão, a ocorrência de microepidemias predominantes em áreas próximas aos ecótopos silvestres pode estar relacionada com a cepa do parasito, tendo-se em conta a predominância do Biodema Tipo III, Z1 nestas áreas. No presente estudo foi investigada a infectividade de cepas do T. cruzi de diferentes biodemas quando inoculadas por via

  14. Experimental Chemotherapy for Chagas Disease: A Morphological, Biochemical, and Proteomic Overview of Potential Trypanosoma cruzi Targets of Amidines Derivatives and Naphthoquinones

    OpenAIRE

    Solange L. de Castro; Denise G. J. Batista; Marcos M. Batista; Wanderson Batista; Anissa Daliry; de Souza, Elen M.; Menna-Barreto, Rubem F. S.; Gabriel M de Oliveira; Kelly Salomão; Silva, Cristiane F.; Silva, Patricia B.; Soeiro, Maria de Nazaré C.

    2011-01-01

    Chagas disease (CD), caused by Trypanosoma cruzi, affects approximately eight million individuals in Latin America and is emerging in nonendemic areas due to the globalisation of immigration and nonvectorial transmission routes. Although CD represents an important public health problem, resulting in high morbidity and considerable mortality rates, few investments have been allocated towards developing novel anti-T. cruzi agents. The available therapy for CD is based on two nitro derivatives (...

  15. Orally-transmitted Chagas disease.

    Science.gov (United States)

    Filigheddu, Maria Teresa; Górgolas, Miguel; Ramos, José Manuel

    2017-02-09

    Chagas disease is a zoonosis caused by protozoan parasite Trypanosoma cruzi, which is most frequently associated with a vectorial transmission. However, in recent years we have observed a significant increase in the oral transmission of the disease, associated mainly with the consumption of drinks made from fruit or other vegetables contaminated with triatomine faeces or secretions from infected mammals. After a latency period of 3 to 22 days after ingestion, the oral infection is characterized by more severe manifestations than those associated with vectorial transmission: prolonged fever, acute myocarditis with heart failure and, in some cases, meningoencephalitis. Mortality can reach up to 33% of those infected. The aim of this paper is to review this matter and to promote prevention practices. Copyright © 2016 Elsevier España, S.L.U. All rights reserved.

  16. Chagas disease in prehistory

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    Luiz F. Ferreira

    2011-09-01

    Full Text Available The classical hypothesis proposes that Chagas disease has been originated in the Andean region among prehistoric people when they started domesticating animals, changing to sedentary habits, and adopting agriculture. These changes in their way of life happened nearly 6,000 years ago. However, paleoparasitological data based on molecular tools showed that Trypanosoma cruzi infection and Chagas disease were commonly found both in South and North American prehistoric populations long before that time, suggesting that Chagas disease may be as old as the human presence in the American continent. The study of the origin and dispersion of Trypanosoma cruzi infection among prehistoric human populations may help in the comprehension of the clinical and epidemiological questions on Chagas disease that still remain unanswered.A hipótese clássica sobre a origem da doença de Chagas propõe que tenha surgido entre as populações pré-históricas dos Andes quando começaram a domesticar animais, mudaram para hábitos sedentários e adotaram a agricultura. Estas mudanças em seus hábitos de vida aconteceram há aproximadamente 6.000 anos. Entretanto, os dados da paleoparasitologia, baseados na biologia molecular, mostraram que a infecção por Trypanosoma cruzi e a doença de Chagas eram comuns tanto em populações pré-históricas da América do Sul e América do Norte muito antes deste período. De acordo com os dados paleoparasitológicos, a doença de Chagas pode ser tão antiga quanto a presença humana no continente americano. O estudo sobre a origem e dispersão da infecção por Trypanosoma cruzi entre populações humanas pré-históricas pode auxiliar na compreensão de questões clínicas e epidemiológicas sobre a doença de Chagas que ainda permanecem sem resposta.

  17. An experimental model of hemolysis-induced acute pancreatitis

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    Saruc M.

    2003-01-01

    Full Text Available The literature indicates that acute pancreatitis is a complication of massive hemolysis with a prevalence of about 20%. We describe an experimental model of hemolysis-induced acute pancreatitis. Hemolytic anemia was induced in rats by a single ip injection of 60 mg/kg of 20 mg/ml acetylphenylhydrazine (APH in 20% (v/v ethanol on the first experimental day (day 0. One hundred and fifty Wistar albino rats weighing 180-200 g were divided into three groups of 50 animals each: groups 1, 2 and 3 were injected ip with APH, 20% ethanol, and physiological saline, respectively. Ten rats from each group were sacrificed on study days 1, 2, 3, 4 and 5. Serum amylase, lipase levels and pancreatic tissue tumor necrosis factor-alpha (TNF-alpha and platelet-activating factor (PAF contents were determined and a histological examination of the pancreas was performed. No hemolysis or pancreatitis was observed in any of the rats in groups 2 and 3. In group 1, massive hemolysis was observed in 35 (70% of 50 rats, moderate hemolysis in seven (14%, and no hemolysis in eight (16%. Thirty-three of 35 (94.2% rats with massive hemolysis had hyperamylasemia, and 29 of these rats (82.8% had histologically proven pancreatitis. The most severe pancreatitis occurred on day 3, as demonstrated by histology. Tissue TNF-alpha and PAF levels were statistically higher in group 1 than in groups 2 and 3. Acute massive hemolysis induced acute pancreatitis, as indicated by histology, in almost 80% of cases. Hemolysis may induce acute pancreatitis by triggering the release of proinflammatory and immunoregulatory cytokines.

  18. Protective effect of aspirin treatment on mouse behavior in the acute phase of experimental infection with Trypanosoma cruzi.

    Science.gov (United States)

    Silvero-Isidre, Arturo; Morínigo-Guayuán, Sergio; Meza-Ojeda, Aaron; Mongelós-Cardozo, Marcelo; Centurión-Wenninger, Claudia; Figueredo-Thiel, Susy; Sanchez, Diego F; Acosta, Nidia

    2018-01-01

    Chagas disease is a potentially fatal disease caused by the parasite Trypanosoma cruzi, which can in some cases affect the central nervous system. The objective was to evaluate the effect of aspirin (ASA) in the behavior of mice infected with T. cruzi during the acute phase. This was an experimental study with random assignation. Twenty four BALB/c mice were divided into four groups of six animals each as follows: only ASA (OA), ASA before infection (BI), ASA after infection (AI) and only infection (OI). The strain used for infection was M/HOM/Bra/53/Y. An ASA dose of 100 mg/kg per day was administered 72 h before infection to BI group and the same dose 48 h after infection to AI group. Mice behavior in the open field test, mortality, and brain histopathology was evaluated. Data were analyzed using ANOVA, chi square test, and Kaplan-Meier with long-rank for survival analysis. In the open field test, the OA group has similar results with the BI group, in the variables of immobility and escape. Also, the OA group displayed significantly higher rates of micturition (p < 0.001) and defecation (p < 0.001) compared to infected groups. Mortality was higher in BI group (p = 0.02). The presence of T. cruzi amastigotes were higher in brain tissues of the AI and OI groups (p = 0.008). In conclusion, the administration of ASA before infection seemed to prevent behavioral changes induced by the acute infection, but it led to accelerated mortality. The study highlighted the potential importance of the pathways inhibited by ASA in the early hours of acute infection with T. cruzi.

  19. Altered Cardiomyocyte Function and Trypanosoma cruzi Persistence in Chagas Disease.

    Science.gov (United States)

    Cruz, Jader Santos; Santos-Miranda, Artur; Sales-Junior, Policarpo Ademar; Monti-Rocha, Renata; Campos, Paula Peixoto; Machado, Fabiana Simão; Roman-Campos, Danilo

    2016-05-04

    Chagas disease, caused by the triatominae Trypanosoma cruzi, is one of the leading causes of heart malfunctioning in Latin America. The cardiac phenotype is observed in 20-30% of infected people 10-40 years after their primary infection. The cardiac complications during Chagas disease range from cardiac arrhythmias to heart failure, with important involvement of the right ventricle. Interestingly, no studies have evaluated the electrical properties of right ventricle myocytes during Chagas disease and correlated them to parasite persistence. Taking advantage of a murine model of Chagas disease, we studied the histological and electrical properties of right ventricle in acute (30 days postinfection [dpi]) and chronic phases (90 dpi) of infected mice with the Colombian strain of T. cruzi and their correlation to parasite persistence. We observed an increase in collagen deposition and inflammatory infiltrate at both 30 and 90 dpi. Furthermore, using reverse transcriptase polymerase chain reaction, we detected parasites at 90 dpi in right and left ventricles. In addition, we observed action potential prolongation and reduced transient outward K(+) current and L-type Ca(2+) current at 30 and 90 dpi. Taking together, our results demonstrate that T. cruzi infection leads to important modifications in electrical properties associated with inflammatory infiltrate and parasite persistence in mice right ventricle, suggesting a causal role between inflammation, parasite persistence, and altered cardiomyocyte function in Chagas disease. Thus, arrhythmias observed in Chagas disease may be partially related to altered electrical function in right ventricle. © The American Society of Tropical Medicine and Hygiene.

  20. Creatine kinase activity in dogs with experimentally induced acute inflammation

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    Dimitrinka Zapryanova

    2013-01-01

    Full Text Available The main purpose of this study was to investigate the effect of acute inflammation on total creatine kinase (CK activity in dogs. In these animals, CK is an enzyme found predominantly in skeletal muscle and significantly elevated serum activity is largely associated with muscle damage. Plasma increases in dogs are associated with cell membrane leakage and will therefore be seen in any condition associated with muscular inflammation. The study was induced in 15 mongrel male dogs (n=9 in experimental group and n=6 in control group at the age of two years and body weight 12-15 kg. The inflammation was reproduced by inoculation of 2 ml turpentine oil subcutaneously in lumbar region. The plasma activity of creatine kinase was evaluated at 0, 6, 24, 48, 72 hours after inoculation and on days 7, 14 and 21 by a kit from Hospitex Diagnostics. In the experimental group, the plasma concentrations of the CK-activity were increased at the 48th hour (97.48±6.92 U/L and remained significantly higher (p<0.05 at the 72 hour (97.43±2.93 U/L compared to the control group (77.08±5.27 U/L. The results of this study suggest that the evaluation of creatine kinase in dogs with experimentally induced acute inflammation has a limited diagnostic value. It was observed that the creatine kinase activity is slightly affected by the experimentally induced acute inflammation in dogs.

  1. O eletrocardiograma na fase crônica da doença de Chagas experimental no cão

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    J. Pellegrino

    1946-03-01

    Full Text Available O Autor estudou o eletrocardiograma de 6 cães adultos antes e após a inoculação, nestes animais, de uma amostra de Schizotrypanum cruzi obtida de um caso humano de miocardite chagásica com bloqueio aurículo-ventricular total. A fase aguda da moléstia nos cães foi seguida por frequentes exames de sangue a fresco, entre lãmina e lamínula, para a pesquisa do flagelado. Os traçados eletrocardiográficos foram obtidos antes da inoculação e até 320 dias após a mesma. Além das derivações periféricas, em alguns cães, registrou também as derivações precordiais. A interpretação dos eletrocardiogramas seriados foi feita levando-se em conta a variabilidade dos traçados em série observada em cães normais. Em todos os 6 cães estudados houve uma diminuição muito acentuada da voltagem dos complexos ventriculares, denotando lesão miocárdica. A diminuição da voltagem de QRs já se evidencia na fase aguda e de transição da moléstia, tornando-se máxima logo no inicio da fase crônica. Em dois cães, paralelamente com a diminuição da voltagem, houve uma rotação do eixo elétrico para a esquerda. Em um cão foram observadas extrasístoles ventriculares e, em dois, extrasístoles auriculares. Somente em um cão observou alterações significativas da onda P. constituidas por alargamento e entalhe da mesma. O Autor salienta e discute o fato de não ter encontrado alterações na condução (não houve aumento de Pr e somente em um caso houve alargamento significativo de QRS. As pesquizas ainda continuam sendo apenas parciais os resultados apresentados. Agradecemos ao Prof. AMERICANO FREIRE pelas sugestões e ao Sr. KURT BENSEMANN pela constante assistencia técnica.The Author has studied the electrocardiograms of 6 adult dogs, before and after the inoculation of a Schizotrypanum cruzi strain in these animals, which has been obtained from a human case of Chagas' myocarditis with complete aurriculoventricular block. The acute

  2. Synthetic antiproteases in acute pancreatitis: an experimental study.

    Science.gov (United States)

    Dobosz, M; Sledziński, Z; Babicki, A; Juszkiewicz, P; Basiński, A; Wajda, Z

    1992-01-01

    Acute pancreatitis was induced in 19 anesthetized dogs by retrograde injection of bile mixed with trypsin into the pancreatic duct. Two groups, of six animals each, were treated with intravenous infusion of synthetic antiproteases: gabexate mesilate and nafamostat mesilate in doses of 1 mg/kg per hr. One group of seven animals remained untreated. Two untreated dogs died during the experiment. All the treated dogs survived. Hemodynamic data were monitored hourly during a 6-hr observation period. In the untreated animals, cardiac output, mean arterial pressure, and left ventricular stroke volume decreased rapidly; an increase of pulmonary vascular resistance and systemic vascular resistance was observed. Synthetic antiproteases, given as a therapy, improved the hemodynamic parameters significantly and prevented the animals from developing shock. Gabexate mesilate and nafamostat mesilate seem to be of value in the treatment of experimentally produced acute pancreatitis in dogs.

  3. [MRI semiotics features of experimental acute intracerebral hematomas].

    Science.gov (United States)

    Burenchev, D V; Skvortsova, V I; Tvorogova, T V; Guseva, O I; Gubskiĭ, L V; Kupriianov, D A; Pirogov, Iu A

    2009-01-01

    The aim of this study was to assess the possibility of revealing intracerebral hematomas (ICH), using MRI, within the first hours after onset and to determine their MRI semiotics features. Thirty animals with experimental ICH were studied. A method of two-stage introduction of autologous blood was used to develop ICH as human spontaneous intracranial hematomas. Within 3-5h after blood introduction to the rat brain. The control MRI was performed in the 3rd and 7th days after blood injections. ICH were definitely identified in the first MRI scans. The MRI semiotics features of acute ICH and their transformations were assessed. The high sensitivity of MRI to ICH as well as the uniform manifestations in all animals were shown. In conclusion, the method has high specificity for acute ICH detection.

  4. Aspectos neurológicos da doença de chagas: sistema nervoso central

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    Sylvio de Vergueiro Forjaz

    1967-09-01

    Full Text Available The lesions of the nervous system in the Trypanosomiasis Cruzi are quite frequent and are not only limited to the encephalo-spinal-axis. Actually, they are much more common in the peripheral representations of the autonomic nervous system, resulting in the so-called enteromegalies (mega-esophagus, megacolon, etc. so frequent in Brazil. However, only the clinical manifestations due to the encephalic and spinal lesions have been included in the neurological aspects of Chagas' disease (as formerly contended for by Carlos Chagas. In the acute phase of the central nervous system infestation, the Trypanosoma cruzi,as leishmanias, is found in cellular elements of the neuroglia (microglia, astroglia and may be isolated from the peripheral blood and cerebrospinal fluid (inoculation in sensitive animals. The corresponding clinical manifestations are the severe difuse meningo-encephalo-myelitis with a high degree of lethality and also signs of infection, hepatomegaly and splenomegaly. The infants from endemic areas are much more compromised. The clinical-pathologic as well as experimental confirmations on that acute phase of the disease are numerous and irrefutable. In the chronic phase of the disease, the neurological manifestations are not very clear. Early in 1909, Chagas, impressed with the great number of cases of infantile encephalopathy found in infested regions, imputed to the T. cruzithe etiology of such cases of encephalopathy and considered them as pertaining to a chronic phase of the disease. This has not been confirmed by other investigations, and even if the etiologic agent were the T. cruzithe clinical manifestations have no evolutive character and seem more sequelae than symptoms of a real chronic nervous phase. Even experimentally it has not been possible to demonstrate the presence of parasites in the nervous system of infested animals after clearing of the signs of the acute phase. In patients with chronic Chagas' disease with lesions in

  5. Immunity in Chagas’ Disease.

    Science.gov (United States)

    This is the final report on the immunity in Chagas ’ disease contract and it summarizes the results of a diversity of studies directed toward...antibody test for Chagas ’ disease . Also mentioned are the facts that the cell membranes of live trypomastigotes are not immunoreactive with the...humoral immune response of an infected host and that suppression of parasitemias in chronic Chagas ’ disease is probably a function of the cell immune system of the host. (Author)

  6. Cholinesterase inhibition reduces arrhythmias in asymptomatic Chagas disease.

    Science.gov (United States)

    Castro, Renata R T; Porphirio, Graciema; Xavier, Sergio S; Moraes, Ruy S; Ferlin, Elton L; Ribeiro, Jorge P; da Nóbrega, Antonio C L

    2017-10-01

    Parasympathetic dysfunction may play a role in the genesis of arrhythmias in Chagas disease. This study evaluates the acute effects of pyridostigmine (PYR), a reversible cholinesterase inhibitor, on the occurrence of arrhythmias in patients with Chagas cardiac disease. Following a double-blind, randomized, placebo-controlled, cross-over protocol, 17 patients (age 50±2 years) with Chagas cardiac disease type B underwent 24-hour Holter recordings after oral administration of either pyridostigmine bromide (45 mg, 3 times/day) or placebo (PLA). Pyridostigmine reduced the 24-hours incidence (median [25%-75%]) of premature ventricular beats-PLA: 2998 (1920-4870), PYR: 2359 (940-3253), P=.044; ventricular couplets-PLA: 84 (15-159), PYR: 33 (6-94), P=.046. Although the total number of nonsustained ventricular tachycardia in the entire group was not different (P=.19) between PLA (1 [0-8]) and PYR (0 [0-4]), there were fewer episodes under PYR in 72% of the patients presenting this type of arrhythmia (P=.033). Acute administration of pyridostigmine reduced the incidence of nonsustained ventricular arrhythmias in patients with Chagas cardiac disease. Further studies that address the use of pyridostigmine by patients with Chagas cardiac disease under a more prolonged follow-up are warranted. © 2017 John Wiley & Sons Ltd.

  7. ECG Changes in Acute Experimental Ruminal Lactic Acidosis in Sheep

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    Zahra Karimi-Dehkordi

    2011-09-01

    Full Text Available AbstractFor induction of ruminal acidosis, 10 clinically healthy three years old non pregnant female sheep were selected. Prior to the infusion of sucrose (0 hour, rumen and blood samples were obtained in order to determine baseline rumen and blood pH, respectively. Electrocardiogram (ECG was also recorded. Acute ruminal acidosis was induced experimentally with sucrose at a dose of 18g kg-1 body weigh through rumen fistula. ECG was recorded and blood and rumen samples collected at 3, 6, 9, 12, 15, 18, 21, 24, 30, 36, and 48 hours after the infusion of sucrose. Results indicated that blood and rumen pH decreased significantly at 15, 18, 21, 24, 30, 36 and 48 hours and at 3, 6, 9, 12, 15, 18, 21, 24, 30, 36 and 48 hours, respectively. Acidosis produced a marked increasing in heart rate and a decrease in PR interval at 15 and 18 hour significantly with little apparent effect on the ST and PR segment. The P amplitude increased significantly at 6, 9, 12, 15, 18, 21, 24 and 30 hours. The T amplitude increased significantly at 9, 12, 15, 18, 21, 24, 30 and 36 hours. The RR interval decreased significantly at 6, 9, 12, 15, 18, 21, 24, 30, 36 and 48 hours. In conclusion acute ruminal acidosis caused significant changes in ECG of sheep though there was not any detectable arrhythmia in the ECG in acute ruminal acidosis.

  8. Molecular Mechanisms of Curcumin Renoprotection in Experimental Acute Renal Injury

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    Youling Fan

    2017-12-01

    Full Text Available As a highly perfused organ, the kidney is especially sensitive to ischemia and reperfusion. Ischemia-reperfusion (IR-induced acute kidney injury (AKI has a high incidence during the perioperative period in the clinic and is an important link in ischemic acute renal failure (IARF. Therefore, IR-induced AKI has important clinical significance and it is necessary to explore to develop drugs to prevent and alleviate IR-induced AKI. Curcumin [diferuloylmethane, 1,7-bis(4-hydroxy-3-methoxiphenyl-1,6-heptadiene-3,5-dione] is a polyphenol compound derived from Curcuma longa (turmeric and was shown to have a renoprotective effect on ischemia-reperfusion injury (IRI in a previous study. However, the specific mechanisms underlying the protective role of curcumin in IR-induced AKI are not completely understood. APPL1 is a protein coding gene that has been shown to be involved in the crosstalk between the adiponectin-signaling and insulin-signaling pathways. In the study, to investigate the molecular mechanisms of curcumin effects in kidney ischemia/reperfusion model, we observed the effect of curcumin in experimental models of IR-induced AKI and we found that curcumin treatment significantly increased the expression of APPL1 and inhibited the activation of Akt after IR treatment in the kidney. Our in vitro results showed that apoptosis of renal tubular epithelial cells was exacerbated with hypoxia-reoxygenation (HR treatment compared to sham control cells. Curcumin significantly decreased the rate of apoptosis in renal tubular epithelial cells with HR treatment. Moreover, knockdown of APPL1 activated Akt and subsequently aggravated apoptosis in HR-treated renal tubular epithelial cells. Conversely, inhibition of Akt directly reversed the effects of APPL1 knockdown. In summary, our study demonstrated that curcumin mediated upregulation of APPL1 protects against ischemia reperfusion induced AKI by inhibiting Akt phosphorylation.

  9. Effect of hyperthermia on experimental acute pancreatitis Efeito da hipertermia na pancreatite aguda experimental

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    José Luiz Jesus de Almeida

    2006-12-01

    Full Text Available BACKGROUD: Recent studies indicate that hyperthermia can change inflammatory mechanisms and protect experimental animals from deleterious effects of secretagogue-induced acute pancreatitis AIM: To evaluate the effects of hyperthermia post-treatment on cerulein-induced acute pancreatitis in rats METHODS: Twenty animals were divided in two groups: group I (n = 10, rats with cerulein-induced acute pancreatitis undergone hyperthermia, and group II (n = 10, animals with cerulein-induced acute pancreatitis that were kept normothermic. In all groups, amylase serum levels, histologic damage, vascular permeability and pancreatic water content were assessed. Acute pancreatitis was induced by administration of two cerulein injections (20 mcg/kg. A single dose of Evans' blue dye was administered along with the second dose of cerulein. All animals also received a subcutaneous injection of saline solution. After this process, animals undergone hyperthermia were heated in a cage with two 100 W lamps. Body temperature was increased to 39.5ºC and maintained at that level for 45 minutes. Normothermia rats were kept at room temperature in a second cage RESULTS: Control animals had typical edema, serum amylase activity and morphologic changes of this acute pancreatitis model. Hyperthermia post-treatment ameliorated the pancreatic edema, whereas the histologic damage and the serum amylase level remained unchanged CONCLUSIONS: The findings suggest a beneficial effect of the thermal stress on inflammatory edema in experimental acute pancreatitis.RACIONAL: Estudos recentes indicam que a hipertermia pode modificar mecanismos inflamatórios e proteger animais experimentais dos efeitos deletérios da pancreatite aguda induzida por secretagogos OBJETIVO: Avaliar a eficácia da hipertermia como tratamento da pancreatite aguda induzida por ceruleína em ratos MÉTODOS: Vinte animais foram divididos em dois grupos: grupo I (n = 10, ratos com pancreatite aguda induzida por

  10. Fexinidazole: a potential new drug candidate for Chagas disease.

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    Maria Terezinha Bahia

    Full Text Available BACKGROUND: New safe and effective treatments for Chagas disease (CD are urgently needed. Current chemotherapy options for CD have significant limitations, including failure to uniformly achieve parasitological cure or prevent the chronic phase of CD, and safety and tolerability concerns. Fexinidazole, a 2-subsituted 5-nitroimidazole drug candidate rediscovered following extensive compound mining by the Drugs for Neglected Diseases initiative and currently in Phase I clinical study for the treatment of human African trypanosomiasis, was evaluated in experimental models of acute and chronic CD caused by different strains of Trypanosoma cruzi. METHODS AND FINDINGS: We investigated the in vivo activity of fexinidazole against T. cruzi, using mice as hosts. The T. cruzi strains used in the study were previously characterized in murine models as susceptible (CL strain, partially resistant (Y strain, and resistant (Colombian and VL-10 strains to the drugs currently in clinical use, benznidazole and nifurtimox. Our results demonstrated that fexinidazole was effective in suppressing parasitemia and preventing death in infected animals for all strains tested. In addition, assessment of definitive parasite clearance (cure through parasitological, PCR, and serological methods showed cure rates of 80.0% against CL and Y strains, 88.9% against VL-10 strain, and 77.8% against Colombian strain among animals treated during acute phase, and 70% (VL-10 strain in those treated in chronic phase. Benznidazole had a similar effect against susceptible and partially resistant T. cruzi strains. Fexinidazole treatment was also shown to reduce myocarditis in all animals infected with VL-10 or Colombian resistant T. cruzi strains, although parasite eradication was not achieved in all treated animals at the tested doses. CONCLUSIONS: Fexinidazole is an effective oral treatment of acute and chronic experimental CD caused by benznidazole-susceptible, partially resistant, and

  11. Acute pulmonary injury induced by experimental muscle trauma.

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    Sombra, Márcia Andréa da Silva Carvalho; Vasconcelos, Marcelo Pinho Pessoa de; Guimarães, Sergio Botelho; Escalante, Rodrigo Dornfeld; Garcia, José Huygens Parente; Vasconcelos, Paulo Roberto Leitão de

    2011-01-01

    To develop an easily reproducible model of acute lung injury due to experimental muscle trauma in healthy rats. Eighteen adult Wistar rats were randomized in 3 groups (n=6): G-1- control, G-2 - saline+trauma and G-3 - dexamethasone+trauma. Groups G-1 and G-2 were treated with saline 2,0 ml i.p; G-3 rats were treated with dexamethasone (DE) (2 mg/kg body weight i.p.). Saline and DE were applied 2h before trauma and 12h later. Trauma was induced in G-2 and G-3 anesthetized (tribromoethanol 97% 100 ml/kg i.p.) rats by sharp section of anterior thigh muscles just above the knee, preserving major vessels and nerves. Tissue samples (lung) were collected for myeloperoxidase (MPO) assay and histopathological evaluation. Twenty-four hours after muscle injury there was a significant increase in lung neutrophil infiltration, myeloperoxidase activity and edema, all reversed by dexamethasone in G-3. Trauma by severance of thigh muscles in healthy rats is a simple and efficient model to induce distant lung lesions.

  12. Ventricular arrhythmias in Chagas disease

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    Marco Paulo Tomaz Barbosa

    2015-02-01

    Full Text Available Sudden death is one of the most characteristic phenomena of Chagas disease, and approximately one-third of infected patients develop life-threatening heart disease, including malignant ventricular arrhythmias. Fibrotic lesions secondary to chronic cardiomyopathy produce arrhythmogenic substrates that lead to the appearance and maintenance of ventricular arrhythmias. The objective of this study is to discuss the main clinical and epidemiological aspects of ventricular arrhythmias in Chagas disease, the specific workups and treatments for these abnormalities, and the breakthroughs needed to determine a more effective approach to these arrhythmias. A literature review was performed via a search of the PubMed database from 1965 to May 31, 2014 for studies of patients with Chagas disease. Clinical management of patients with chronic Chagas disease begins with proper clinical stratification and the identification of individuals at a higher risk of sudden cardiac death. Once a patient develops malignant ventricular arrhythmia, the therapeutic approach aims to prevent the recurrence of arrhythmias and sudden cardiac death by the use of implantable cardioverter defibrillators, antiarrhythmic drugs, or both. In select cases, invasive ablation of the reentrant circuit causing tachycardia may be useful. Ventricular arrhythmias are important manifestations of Chagas cardiomyopathy. This review highlights the absence of high-quality evidence regarding the treatment of ventricular arrhythmias in Chagas disease. Recognizing high-risk patients who require specific therapies, especially invasive procedures such as the implantation of cardioverter defibrillators and ablative approaches, is a major challenge in clinical practice.

  13. O etanercepte induz QRS de baixa tensão e disfunção autonômica em camundongos com doença de Chagas experimental

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    Héctor Rodríguez-Angulo

    2013-09-01

    Full Text Available FUNDAMENTO: A doença de Chagas é uma doença parasitária tropical causada pelo protozoário flagelado Trypanosoma cruzi. A cardiomiopatia chagásica é caracterizada por distúrbios na regulação autonômica e na condução do potencial de ação nas fases aguda e crônica da infecção. Embora o fator de necrose tumoral alfa (TNF-α tenha sido associadoà cardiomiopatia em modelos experimentais e em pacientes com doença de Chagas, outros relatos sugerem que o TNF-α pode exercer ações antiparasitárias durante a fase aguda da infecção. OBJETIVOS: Este estudo teve como objetivo determinar os efeitos de um blocker TNF-α solúvel, o etanercepte, em parâmetros eletrocardiográficos na fase aguda da infecção experimental com Trypanosoma cruzi. MÉTODOS: Foram feitos eletrocardiogramas em camundongos infectados não tratados e camundongos infectados que foram tratados com etanercepte 7 dias após a infecção. Os parâmetros de variabilidade onda do eletrocardiograma e frequência cardíaca foram determinados utilizando o Chart para Windows. RESULTADOS: O tratamento com etanercepte resultou em uma baixa tensão do complexo QRS e uma redução da variabilidade da frequência cardíaca em comparação com a ausência de tratamento. No entanto, os camundongos tratados apresentaram um atraso na queda da curva de sobrevivência durante a fase aguda. CONCLUSÃO: Os resultados deste estudo sugerem que, embora o tratamento com etanercepte promova a sobrevivência em camundongos infectados com uma linhagem virulenta de T. cruzi, o bloqueio do TNF-α gera um complexo de baixa tensão e disfunção autonômica durante a fase aguda da infecção. Esses resultados indicam que a mortalidade durante a fase aguda pode ser atribuída a uma resposta inflamatória sistêmica, em vez da disfunção cardíaca.

  14. Experimental Chemotherapy for Chagas Disease: A Morphological, Biochemical, and Proteomic Overview of Potential Trypanosoma cruzi Targets of Amidines Derivatives and Naphthoquinones.

    Science.gov (United States)

    de Castro, Solange L; Batista, Denise G J; Batista, Marcos M; Batista, Wanderson; Daliry, Anissa; de Souza, Elen M; Menna-Barreto, Rubem F S; Oliveira, Gabriel M; Salomão, Kelly; Silva, Cristiane F; Silva, Patricia B; Soeiro, Maria de Nazaré C

    2011-01-01

    Chagas disease (CD), caused by Trypanosoma cruzi, affects approximately eight million individuals in Latin America and is emerging in nonendemic areas due to the globalisation of immigration and nonvectorial transmission routes. Although CD represents an important public health problem, resulting in high morbidity and considerable mortality rates, few investments have been allocated towards developing novel anti-T. cruzi agents. The available therapy for CD is based on two nitro derivatives (benznidazole (Bz) and nifurtimox (Nf)) developed more than four decades ago. Both are far from ideal due to substantial secondary side effects, limited efficacy against different parasite isolates, long-term therapy, and their well-known poor activity in the late chronic phase. These drawbacks justify the urgent need to identify better drugs to treat chagasic patients. Although several classes of natural and synthetic compounds have been reported to act in vitro and in vivo on T. cruzi, since the introduction of Bz and Nf, only a few drugs, such as allopurinol and a few sterol inhibitors, have moved to clinical trials. This reflects, at least in part, the absence of well-established universal protocols to screen and compare drug activity. In addition, a large number of in vitro studies have been conducted using only epimastigotes and trypomastigotes instead of evaluating compounds' activities against intracellular amastigotes, which are the reproductive forms in the vertebrate host and are thus an important determinant in the selection and identification of effective compounds for further in vivo analysis. In addition, due to pharmacokinetics and absorption, distribution, metabolism, and excretion characteristics, several compounds that were promising in vitro have not been as effective as Nf or Bz in animal models of T. cruzi infection. In the last two decades, our team has collaborated with different medicinal chemistry groups to develop preclinical studies for CD and

  15. Experimental Chemotherapy for Chagas Disease: A Morphological, Biochemical, and Proteomic Overview of Potential Trypanosoma cruzi Targets of Amidines Derivatives and Naphthoquinones

    Directory of Open Access Journals (Sweden)

    Solange L. de Castro

    2011-01-01

    Full Text Available Chagas disease (CD, caused by Trypanosoma cruzi, affects approximately eight million individuals in Latin America and is emerging in nonendemic areas due to the globalisation of immigration and nonvectorial transmission routes. Although CD represents an important public health problem, resulting in high morbidity and considerable mortality rates, few investments have been allocated towards developing novel anti-T. cruzi agents. The available therapy for CD is based on two nitro derivatives (benznidazole (Bz and nifurtimox (Nf developed more than four decades ago. Both are far from ideal due to substantial secondary side effects, limited efficacy against different parasite isolates, long-term therapy, and their well-known poor activity in the late chronic phase. These drawbacks justify the urgent need to identify better drugs to treat chagasic patients. Although several classes of natural and synthetic compounds have been reported to act in vitro and in vivo on T. cruzi, since the introduction of Bz and Nf, only a few drugs, such as allopurinol and a few sterol inhibitors, have moved to clinical trials. This reflects, at least in part, the absence of well-established universal protocols to screen and compare drug activity. In addition, a large number of in vitro studies have been conducted using only epimastigotes and trypomastigotes instead of evaluating compounds' activities against intracellular amastigotes, which are the reproductive forms in the vertebrate host and are thus an important determinant in the selection and identification of effective compounds for further in vivo analysis. In addition, due to pharmacokinetics and absorption, distribution, metabolism, and excretion characteristics, several compounds that were promising in vitro have not been as effective as Nf or Bz in animal models of T. cruzi infection. In the last two decades, our team has collaborated with different medicinal chemistry groups to develop preclinical studies

  16. Aspirin treatment of mice infected with Trypanosoma cruzi and implications for the pathogenesis of Chagas disease.

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    Shankar Mukherjee

    2011-02-01

    Full Text Available Chagas disease, caused by infection with Trypanosoma cruzi, is an important cause of cardiovascular disease. It is increasingly clear that parasite-derived prostaglandins potently modulate host response and disease progression. Here, we report that treatment of experimental T. cruzi infection (Brazil strain beginning 5 days post infection (dpi with aspirin (ASA increased mortality (2-fold and parasitemia (12-fold. However, there were no differences regarding histopathology or cardiac structure or function. Delayed treatment with ASA (20 mg/kg beginning 60 dpi did not increase parasitemia or mortality but improved ejection fraction. ASA treatment diminished the profile of parasite- and host-derived circulating prostaglandins in infected mice. To distinguish the effects of ASA on the parasite and host bio-synthetic pathways we infected cyclooxygenase-1 (COX-1 null mice with the Brazil-strain of T. cruzi. Infected COX-1 null mice displayed a reduction in circulating levels of thromboxane (TXA(2 and prostaglandin (PGF(2α. Parasitemia was increased in COX-1 null mice compared with parasitemia and mortality in ASA-treated infected mice indicating the effects of ASA on mortality potentially had little to do with inhibition of prostaglandin metabolism. Expression of SOCS-2 was enhanced, and TRAF6 and TNFα reduced, in the spleens of infected ASA-treated mice. Ablation of the initial innate response to infection may cause the increased mortality in ASA-treated mice as the host likely succumbs more quickly without the initiation of the "cytokine storm" during acute infection. We conclude that ASA, through both COX inhibition and other "off-target" effects, modulates the progression of acute and chronic Chagas disease. Thus, eicosanoids present during acute infection may act as immunomodulators aiding the transition to and maintenance of the chronic phase of the disease. A deeper understanding of the mechanism of ASA action may provide clues to the

  17. Aspirin treatment of mice infected with Trypanosoma cruzi and implications for the pathogenesis of Chagas disease.

    Science.gov (United States)

    Mukherjee, Shankar; Machado, Fabiana S; Huang, Huang; Oz, Helieh S; Jelicks, Linda A; Prado, Cibele M; Koba, Wade; Fine, Eugene J; Zhao, Dazhi; Factor, Stephen M; Collado, J Elias; Weiss, Louis M; Tanowitz, Herbert B; Ashton, Anthony W

    2011-02-15

    Chagas disease, caused by infection with Trypanosoma cruzi, is an important cause of cardiovascular disease. It is increasingly clear that parasite-derived prostaglandins potently modulate host response and disease progression. Here, we report that treatment of experimental T. cruzi infection (Brazil strain) beginning 5 days post infection (dpi) with aspirin (ASA) increased mortality (2-fold) and parasitemia (12-fold). However, there were no differences regarding histopathology or cardiac structure or function. Delayed treatment with ASA (20 mg/kg) beginning 60 dpi did not increase parasitemia or mortality but improved ejection fraction. ASA treatment diminished the profile of parasite- and host-derived circulating prostaglandins in infected mice. To distinguish the effects of ASA on the parasite and host bio-synthetic pathways we infected cyclooxygenase-1 (COX-1) null mice with the Brazil-strain of T. cruzi. Infected COX-1 null mice displayed a reduction in circulating levels of thromboxane (TX)A(2) and prostaglandin (PG)F(2α). Parasitemia was increased in COX-1 null mice compared with parasitemia and mortality in ASA-treated infected mice indicating the effects of ASA on mortality potentially had little to do with inhibition of prostaglandin metabolism. Expression of SOCS-2 was enhanced, and TRAF6 and TNFα reduced, in the spleens of infected ASA-treated mice. Ablation of the initial innate response to infection may cause the increased mortality in ASA-treated mice as the host likely succumbs more quickly without the initiation of the "cytokine storm" during acute infection. We conclude that ASA, through both COX inhibition and other "off-target" effects, modulates the progression of acute and chronic Chagas disease. Thus, eicosanoids present during acute infection may act as immunomodulators aiding the transition to and maintenance of the chronic phase of the disease. A deeper understanding of the mechanism of ASA action may provide clues to the differences

  18. [Chagas disease and immunodeficiency: HIV infection and transplantation].

    Science.gov (United States)

    Le Loup, G; Ibrahim, K; Malvy, D

    2009-12-01

    In the immunocompromised patients, the main features of Chagas disease are severe clinical manifestations during the acute phase and reactivations occurring during the chronic phase. Reactivation is defined by a demonstration of trypomastigots on microscopic examination of blood or the identification of amastigots on biopsy samples and/or acute clinical manifestations during the chronic phase. In HIV patients, meningo-encephalitis and myocarditis are the major clinical syndromes of reactivation. In transplanted patients, cutaneous lesions often reveal the reactivation. A parasiticidal treatment (nifurtimox or benznidazole) should be initiated immediately. A secondary prophylaxis is indicated for HIV patients with CD4 cells count < 200/mm3. In the near future, quantitative PCR could allow to diagnose early reactivation, to initiate preemptive therapy and to closely monitor the therapeutic response. Due to the severe manifestations and prognosis of Chagas disease in the immunocompromised host, two serologic tests must be performed in the patient with an history of residency in endemic countries.

  19. Apendicite aguda: modelo experimental em coelhos Acute appendicitis: model experimental in rabbits

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    João EBRAM-NETO

    2000-04-01

    Full Text Available Com objetivo de estudar experimentalmente as diversas fases evolutivas da apendicite aguda, foram utilizados 60 coelhos (Oryctogalus cuniculus, fêmeas, da linhagem Nova Zelândia, com peso variando de 2510 a 3040 gramas. Os animais foram divididos em dois grupos denominados controle e experimento, e estes subdivididos em três subgrupos com períodos de observação de 12, 24 e 48 horas. No grupo experimento foi realizada a oclusão do lume apendicular por meio de sutura seromuscular circular a 8 cm da extremidade distal do apêndice cecal, com fio de polipropileno 4-0. No controle foi feita somente a simulação da cirurgia. Os aspectos macroscópicos (aumento do tamanho, necrose, perfuração, aderência e secreção na cavidade abdominal bem como os microscópicos do grupo experimento, evidenciaram uma progressão das alterações anatomopatológicas mostrando haver uma relação entre a intensidade dos achados histopatológicos e o tempo de observação. Conclui-se que o método utilizado causa apendicite aguda com alterações anatomopatológicas distintas, de acordo com a fase evolutiva da doença.The evolving phases of acute appendicitis were studied experimentally. Sixty female rabbits (Oryctogalus cuniculus of New Zealand lineage weighing about 2510 to 3040 g were divided in two groups: a control group and experimental group. The experimental group was divided into three subgroups for observation after 12, 24 and 48 hours of the operation, that consisted on a 4-0 polypropylene circular suture at 8 cm from the distal part of the cecal appendix. The control group was sham operated. The macroscopic exam (increase of the appendix volume, necrosis, perfuration, adherence and secretion in the abdominal cavity and the microscopic finding showed a progression in the anatomopathological alterations. There was a close relationship between the histopathological findings and time after the appendiceal obstruction. We conclude that the method

  20. The Role of Eugenol in the Prevention of Acute Pancreatitis-Induced Acute Kidney Injury: Experimental Study

    Science.gov (United States)

    Markakis, Charalampos; Tsaroucha, Alexandra; Papalois, Apostolos E.; Lambropoulou, Maria; Spartalis, Eleftherios; Tsigalou, Christina; Romanidis, Konstantinos; Simopoulos, Constantinos

    2016-01-01

    Aim. Acute pancreatitis is an inflammatory intra-abdominal disease, which takes a severe form in 15–20% of patients and can result in high mortality especially when complicated by acute renal failure. The aim of this study is to assess the possible reduction in the extent of acute kidney injury after administration of eugenol in an experimental model of acute pancreatitis. Materials and Methods. 106 male Wistar rats weighing 220–350 g were divided into 3 groups: (1) Sham, with sham surgery; (2) Control, with induction of acute pancreatitis, through ligation of the biliopancreatic duct; and (3) Eugenol, with induction of acute pancreatitis and eugenol administration at a dose of 15 mg/kg. Serum urea and creatinine, histopathological changes, TNF-α, IL-6, and MPO activity in the kidneys were evaluated at predetermined time intervals. Results. The group that was administered eugenol showed milder histopathological changes than the Control group, TNF-α activity was milder in the Eugenol group, and there was no difference in activity for MPO and IL-6. Serum urea and creatinine levels were lower in the Eugenol group than in the Control group. Conclusions. Eugenol administration was protective for the kidneys in an experimental model of acute pancreatitis in rats. PMID:26884642

  1. Chagas disease: Present status of pathogenic mechanisms and chemotherapy

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    Juan Diego Maya

    2010-01-01

    Full Text Available There are approximately 7.8 million people in Latin America, including Chile, who suffer from Chagas disease and another 28 million who are at risk of contracting it. Chagas is caused by the flagellate protozoan Trypanosoma cruzi. It is a chronic disease, where 20%-30% of infected individuals develop severe cardiopathy, with heart failure and potentially fatal arrhythmias. Currently, Chagas disease treatment is more effective in the acute phase, but does not always produce complete parasite eradication during indeterminate and chronic phases. At present, only nifurtimox or benznidazole have been proven to be superior to new drugs being tested. Therefore, it is necessary to find alternative approaches to treatment of chronic Chagas. The current treatment may be rendered more effective by increasing the activity of anti-Chagasic drugs or by modifying the host's immune response. We have previously shown that glutathione synthesis inhibition increases nifurtimox and benznidazole activity. In addition, there is increasing evidence that cyclooxygenase inhibitors present an important effect on T. cruzi infection. Therefore, we found that aspirin reduced the intracellular infection in RAW 264.7 cells and, decreased myocarditis extension and mortality rates in mice. However, the long-term benefit of prostaglandin inhibition for Chagasic patients is still unknown.

  2. Pathogenesis of Chagas' Disease: Parasite Persistence and Autoimmunity

    Science.gov (United States)

    Teixeira, Antonio R. L.; Hecht, Mariana M.; Guimaro, Maria C.; Sousa, Alessandro O.; Nitz, Nadjar

    2011-01-01

    Summary: Acute Trypanosoma cruzi infections can be asymptomatic, but chronically infected individuals can die of Chagas' disease. The transfer of the parasite mitochondrial kinetoplast DNA (kDNA) minicircle to the genome of chagasic patients can explain the pathogenesis of the disease; in cases of Chagas' disease with evident cardiomyopathy, the kDNA minicircles integrate mainly into retrotransposons at several chromosomes, but the minicircles are also detected in coding regions of genes that regulate cell growth, differentiation, and immune responses. An accurate evaluation of the role played by the genotype alterations in the autoimmune rejection of self-tissues in Chagas' disease is achieved with the cross-kingdom chicken model system, which is refractory to T. cruzi infections. The inoculation of T. cruzi into embryonated eggs prior to incubation generates parasite-free chicks, which retain the kDNA minicircle sequence mainly in the macrochromosome coding genes. Crossbreeding transfers the kDNA mutations to the chicken progeny. The kDNA-mutated chickens develop severe cardiomyopathy in adult life and die of heart failure. The phenotyping of the lesions revealed that cytotoxic CD45, CD8+ γδ, and CD8α+ T lymphocytes carry out the rejection of the chicken heart. These results suggest that the inflammatory cardiomyopathy of Chagas' disease is a genetically driven autoimmune disease. PMID:21734249

  3. Experimental benznidazole treatment of Trypanosoma cruzi II strains isolated from children of the Jequitinhonha Valley, Minas Gerais, Brazil, with Chagas disease

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    Jaquelline Carla Valamiel de Oliveira-Silva

    2015-02-01

    Full Text Available Trypanosoma cruzi strains from distinct geographic areas show differences in drug resistance and association between parasites genetic and treatment response has been observed. Considering that benznidazole (BZ can reduce the parasite burden and tissues damage, even in not cured animals and individuals, the goal is to assess the drug response to BZ of T. cruzi II strains isolated from children of the Jequitinhonha Valley, state of Minas Gerais, Brazil, before treatment. Mice infected and treated with BZ in both phases of infection were compared with the untreated and evaluated by fresh blood examination, haemoculture, polymerase chain reaction, conventional (ELISA and non-conventional (FC-ALTA serologies. In mice treated in the acute phase, a significant decrease in parasitaemia was observed for all strains. Positive parasitological and/or serological tests in animals treated during the acute and chronic (95.1-100% phases showed that most of the strains were BZ resistant. However, beneficial effect was demonstrated because significant reduction (p < 0.05% and/or suppression of parasitaemia was observed in mice infected with all strains (acute phase, associated to reduction/elimination of inflammation and fibrosis for two/eight strains. BZ offered some benefit, even in not cured animals, what suggest that BZ use may be recommended at least for recent chronic infection of the studied region.

  4. [Chronic Chagas cardiomyopathy detected in patients at the Regional General Hospital O'Horan, Merida, Yucatan, Mexico].

    Science.gov (United States)

    Zavala-Castro, J E; Gutiérrez-Flota, H; Barrera-Pérez, M A; Bolio-Solís, A de J; Zavala-Velázquez, J E

    1995-01-01

    The purpose of this study was to determine the frequency of cardiopathy due to Chagas' disease in 36 patients of the cardiology department at the Regional General Hospital O'Horan in Merida, Yucatan. All patients included in the study had cardiac involvement compatible with acute or chronic stages of Chagas' disease. Medical records prepared for each one of the patients included a Chagas' disease targeted clinical history, chest X-ray, electrocardiogram, blood culture and serology using indirect immunofluorescence test. Out of the 36 patients studied, 7 were diagnosed as having Chagas' disease cardiopathy. Grade II cardiomegaly was established in 2 patients while the remaining 5 had grade III cardiomegaly. Conduction abnormalities were established in 6 patients while 2 of these had evidence of necrosis and/or ischemia. Chagas' disease cardiopathy, as our results suggest, is not a rare event in the cardiology ward at the O'Horan Hospital.

  5. A Critical Review on Chagas Disease Chemotherapy

    Directory of Open Access Journals (Sweden)

    Coura José Rodrigues

    2002-01-01

    Full Text Available In this "Critical Review" we made a historical introduction of drugs assayed against Chagas disease beginning in 1912 with the works of Mayer and Rocha Lima up to the experimental use of nitrofurazone. In the beginning of the 70s, nifurtimox and benznidazole were introduced for clinical treatment, but results showed a great variability and there is still a controversy about their use for chronic cases. After the introduction of these nitroheterocycles only a few compounds were assayed in chagasic patients. The great advances in vector control in the South Cone countries, and the demonstration of parasite in chronic patients indicated the urgency to discuss the etiologic treatment during this phase, reinforcing the need to find drugs with more efficacy and less toxicity. We also review potential targets in the parasite and present a survey about new classes of synthetic and natural compounds studied after 1992/1993, with which we intend to give to the reader a general view about experimental studies in the area of the chemotherapy of Chagas disease, complementing the previous papers of Brener (1979 and De Castro (1993.

  6. Chagas Heart Disease: An Update.

    Science.gov (United States)

    Malik, Lindsey H; Singh, Gagan D; Amsterdam, Ezra A

    2015-11-01

    Chagas disease, also known as American trypanosomiasis, results from infection by the protozoan Trypanosoma cruzi, and is a major cause of cardiac disease worldwide. Until recently, Chagas disease was confined to those areas of South and Central America where Trypanosoma cruzi is endemic. With the migration of infected individuals, however, the disease has spread, and it is estimated that 6-7 million people worldwide are infected. In the US alone, more than 7 million people from Trypanosoma cruzi-endemic countries became legal US residents by the turn of the century, resulting in a surge of Chagas disease in this country. According to preliminary estimates, the US now ranks seventh in the Western Hemisphere in number of individuals infected with Trypanosoma cruzi, and the disease has become a major public health concern due to limited awareness in the medical community. Copyright © 2015 Elsevier Inc. All rights reserved.

  7. A doença de Chagas em Minas Gerais: esbôco crítico dos trabalhos publicados até 1951 Chagas' disease in Minas Geraes: a critical sudy of the papers published up to 1951

    Directory of Open Access Journals (Sweden)

    J. Pellegrino

    1953-12-01

    Lassance were carried out by Chagas and its co-workers of the Oswaldo Cruz Institute. During this period they described the various clinical features of the new disease, made a detailed study of its agent and the biology of the transmitting insects, and experiments and studies on the pathogeny and pathology of the disease; they developed diagnostic methods, analysed the role of domiciliary and wild reservoirs, and insistently showed the social significance of this sanitary problem. 2 The research work made on Chagas' disease in Bambuí contributed decisively for the growing interest on the study of this disease during the last few years. Although the work in Bambuí was carried out continuously since its beginning in 1940, the researches may be divided into two groups, namely the preliminary made before the installation in the mentioned city of the Center for the Study and Prophylaxis of Chagas' Disease in November 1943, and the work done after the installation of the Center. The first group represents the first contribution after the researches carried out in Lassance, towards a formal study of acute cases of Chagas' disease in the State .The finding of numerous acute cases at Bambuí led the direction of the Oswaldo Cruz Institute to create a Center of Studies in that city. An outstanding contribution on the clinical, epidemiological and prophylactic fields was brought about by investigators of Manguinhos with the abundant material supplied by the Bambuí Center. The chief contributions from Bambuí were of three kinds: a The individualization of the chronic Chagas' heart disease on clinical, anatomo-pathological, electrocardiographic and experimental basis; the demonstration of its great frequency in infected individuals and the verification that in certain rural areas schizotrypanosis is one of the most important etiological factors of heart disease. b The experience acquired with the use of the complement fixation reaction with antigens of cultures of Schizotripanum

  8. Experimental model of severe acute pancreatitis in rabbits Modelo experimental de pancreatite aguda grave em coelhos

    Directory of Open Access Journals (Sweden)

    Alberto Goldenberg

    2007-10-01

    Full Text Available PURPOSE: To develop an experimental model of severe acute pancreatitis in rabbits through a pancreatic ductal injection of sodium taurocholate. METHODS: Twenty-four albino rabbits of the New Zealand lineage were distributed into four groups of six animals (A, B, C and S. The rabbits of three experimental groups (A, B and C were submitted to a laparatomy and received a pancreatic ductal injection of 1ml/kg sodium taurocholate 5%. Also, they were submitted to further laparatomies after 4h, 8h and 12h, respectively. The control group (S was subdivided into two groups of three animals: in subgroup S1 only the pancreatic duct catheterization was performed whereas in subgroup S2 the pancreatic duct catheterization as well as an injection of 1ml/kg physiologic solution 0.9% were carried out. After 12 hours, the rabbits were evaluated. In the re-intervention, blood was collected to determine the amylasemia and a pancreatectomy was carried out to investigate interstitial infiltration, steatonecrosis and necrosis of the organ, using an optical microscope. RESULTS: There was an elevation of amylase in all groups thus proving the existence of acute pancreatitis. The size of the interlobular septum increased progressively with a greater variation between group S1 (0.13 and group C (0. 53 (p=0.035. While all the animals in group A exhibited focal cellular necrosis, it was more intense in the rabbits of group B and culminated with a high proportion of severe pancreatic necrosis in group C animals. The difference in the intensity of cellular necrosis showed statistic significance (p=0.001. CONCLUSION: The proposed experimental model demonstrated its reproducibility and effectiveness in producing severe acute pancreatitis in rabbits.OBJETIVO: Desenvolver modelo experimental de pancreatite aguda grave em coelhos por meio da injeção de taurocolato de sódio no ducto pancreático. MÉTODOS: Vinte e quatro coelhos albinos da linhagem Nova Zelândia foram distribu

  9. Strategies to improve oxygenation in experimental acute lung injury

    NARCIS (Netherlands)

    A. Hartog (Arthur)

    2000-01-01

    textabstractOne of the most important clinical syndromes, in which failure of oxygen uptake in the lung leads to severe hypoxia, is the so-called acute respiratory distress syndrome (ARDS). ARDS is a complex of clinical signs and symptoms which occur following diverse pulmonary or systemic insults,

  10. Failure of experimental acute intra-gastric gas and fluid ...

    African Journals Online (AJOL)

    The stomachs of 6 mongrel dogs were cannulated with a simple assemblage of cannula and sphygmomanometer for direct and rapid administration of gas and combination of gas and fluid, respectively, to investigate the role of intra-gastric accumulation of gas and fluid in the stomach in development of acute gastric ...

  11. Chagas disease: control, elimination and eradication. Is it possible?

    Directory of Open Access Journals (Sweden)

    Jose Rodrigues Coura

    2013-12-01

    Full Text Available From an epidemiological point of view, Chagas disease and its reservoirs and vectors can present the following characteristics: (i enzooty, maintained by wild animals and vectors, with broad occurrence from southern United States of America (USA to southern Argentina and Chile (42ºN 49ºS, (ii anthropozoonosis, when man invades the wild ecotope and becomes infected with Trypanosoma cruzi from wild animals or vectors or when the vectors and wild animals, especially marsupials, invade the human domicile and infect man, (iii zoonosis-amphixenosis and exchanged infection between animals and humans by domestic vectors in endemic areas and (iv zooanthroponosis, infection that is transmitted from man to animals, by means of domestic vectors, which is the rarest situation in areas endemic for Chagas disease. The characteristics of Chagas disease as an enzooty of wild animals and as an anthropozoonosis are seen most frequently in the Brazilian Amazon and in the Pan-Amazon region as a whole, where there are 33 species of six genera of wild animals: Marsupialia, Chiroptera, Rodentia, Edentata (Xenarthra, Carnivora and Primata and 27 species of triatomines, most of which infected with T. cruzi . These conditions place the resident populations of this area or its visitors - tourists, hunters, fishermen and especially the people whose livelihood involves plant extraction - at risk of being affected by Chagas disease. On the other hand, there has been an exponential increase in the acute cases of Chagas disease in that region through oral transmission of T. cruzi , causing outbreaks of the disease. In four seroepidemiological surveys that were carried out in areas of the microregion of the Negro River, state of Amazonas, in 1991, 1993, 1997 and 2010, we found large numbers of people who were serologically positive for T. cruzi infection. The majority of them and/or their relatives worked in piassava extraction and had come into contact with and were stung by

  12. Changes of Prooxidant-Antioxidant Systems in Experimental Acute Pancreatitis

    Directory of Open Access Journals (Sweden)

    Viktoria Cherkasova

    2017-10-01

    Full Text Available Mortality in acute destructive pancreatitis, despite the development and introduction of new methods of treatment, remains stable high and in severe forms reaches 25-85%. Activation of neutrophils and macrophages in acute pancreatitis leads to an "oxygen burst", which is closely linked with the activation of lipid peroxidation. Goals. The purpose is to establish dynamic changes in the indexes of prooxidant-antioxidant systems in acute L-arginine-induced pancreatitis. Materials and methods. The study was performed on 62 white male rats of Wistar line weighing 180-220g, with modeled acute pancreatitis. Blood for analysis have been taken: the blood serum on 12, 24, 48 and 72 hours of experiment to determine the activity level of thiobarbituric acid products, diene conjugates, catalase and lactate for assessment of the intensity of oxidative stress and antioxidant systems. Results. The obtained results of the study showed that acute L-arginine-induced pancreatitis is accompanied by an intensification of lipid peroxidation processes (LPO. Revealed that the most pronounced increase in all blood parameters is observed 24 hours after the beginning of the study. A significant increase in the active products of tiobarbituric acid (TBA-AP and diene conjugates (DC was detected - 1.98 and 2.7 times, respectively, and 2.2 times the growth of catalase (CT. At the next stage of the experiment there is a slowdown in the rate of LPO, as evidenced by the following values. Thus, for 48 years in the 3rd group: TBA-AP - they increased by 5.1% (p> 0.05, DC - by 3.3% (p> 0.05, and the level of CT - by 43.4% (P 0.05, which may indicate an exhaustion of antioxidant systems. Indicators of LPO on 72 hours compared with 48 hours in group III: TBA-AP - increased by 1.7% (p> 0.05, DC - by 5.7% (p> 0.05. Conclusions. Acute L-arginine-induced pancreatitis is accompanied by an intensification of lipid peroxidation-oxidation processes that can potentiate the development of

  13. New Scenarios of Chagas Disease Transmission in Northern Colombia

    Directory of Open Access Journals (Sweden)

    Catalina Tovar Acero

    2017-01-01

    Full Text Available Chagas disease (CD is a systemic parasitic infection caused by the flagellated form of Trypanosoma cruzi. Córdoba department, located in the Colombian Caribbean Coast, was not considered as a region at risk of T. cruzi transmission. In this article, we describe the first acute CD case in Salitral village in Sahagún, Córdoba, confirmed by microscopy and serological tests. Our results draw attention to a new scenario of transmission of acute CD in nonendemic areas of Colombia and highlight the need to include CD in the differential diagnosis of febrile syndromes in this region.

  14. Chagas Disease: No Longer Exotic

    Centers for Disease Control (CDC) Podcasts

    2008-04-03

    This podcast is designed to inform health care providers about Chagas disease, diagnosis, and treatment and to assist in identifying infected patients.  Created: 4/3/2008 by National Center for Zoonotic, Vector-Borne, and Enteric Diseases (NCZVED).   Date Released: 4/8/2008.

  15. Active transmission of human chagas disease in Colima Mexico

    Directory of Open Access Journals (Sweden)

    Rafael Coll-Cárdenas

    2004-06-01

    Full Text Available Despite efforts to eradicate American trypanosomiasis (AT and Chagas disease from the Americas, there are still areas of active transmission that can eventually become a source of reinfection in previously controlled regions. Mexico could be one of those areas, where there are no formal preventive control programs despite the presence of communities infested by Triatominae bugs infected with Trypanosoma cruzi. This study explored the prevalence of T. cruzi infection in 405 habitants of 17 communities in the state of Colima, on the Pacific Mexican coast, through a seroepidemiological probabilistic survey. The results revealed a point seroprevalence of 2.4% positive for anti-T. cruzi. In addition, 2 clinical cases of chronic and 2 of acute Chagas disease were detected in the explored communities. These findings confirm the risk of active transmission of AT in Western Mexico, especially in rural and suburban communities infested with intra-domestic triatominae, where control programs should be implemented.

  16. The effect of menthol on acute experimental colitis in rats.

    Science.gov (United States)

    Ghasemi-Pirbaluti, Masoumeh; Motaghi, Ehsan; Bozorgi, Homan

    2017-06-15

    Menthol is an aromatic compound with high antiinflammatory activity. The purpose of the current research is to investigate the effectiveness of menthol on acetic acid induced acute colitis in rats. Animals were injected with menthol (20 and 50 and 80mg/kg, i.p.) 24h prior to induction of colitis for 3 consecutive days. Menthol at medium and higher doses similar to dexamethasone as a reference drug significantly reduced body weight loss, macroscopic damage score, ulcer area, colon weight, colon length and improved hematocrit in rats with colitis. The histopathological examination also confirmed anti-colitic effects of menthol. Menthol also reduced significantly the colonic levels of tumor necrosis factor-α (TNF-α), interleukin 1β (IL-1β), interleukin 6 (IL-6) and myeloperoxidase (MPO) activity in inflamed colons. Thus, the findings of the current study provide evidence that menthol may be beneficial in patients suffering from acute ulcerative colitis. Copyright © 2017 Elsevier B.V. All rights reserved.

  17. Experimental model of intracranial arteriovenous shunting in the acute stage.

    Science.gov (United States)

    Numazawa, Shinichi; Sasaki, Tatsuya; Sato, Sonomi; Watanabe, Yoichi; Watanabe, Zenichiro; Kodama, Namio

    2005-06-01

    A model of intracranial arteriovenous (AV) shunting must incorporate local hypoperfusion and simulate the hemodynamics of arteriovenous malformations. In this study, the hemodynamics of an intracranial AV shunt model in the acute stage were clarified. End-to-side anastomoses with a femoral vein graft were performed between a cortical branch of the middle cerebral artery (MCA) and the superior sagittal sinus in anesthetized dogs. Local cerebral blood flow (l-CBF) was measured by laser Doppler blood flowmetry. l-CBF decreased suddenly by 34.2% when the shunt was opened in the ipsilateral MCA territory. Upon re-occlusion, l-CBF immediately equaled or exceeded the pre-opening value and returned to the pre-opening value within the next 15 minutes. Opening the shunt produced little change in l-CBF in the territory of the ipsilateral or contralateral anterior cerebral artery. The decrease in l-CBF was correlated with shunt volume only in the MCA territory. l-CBF manifested a PaCO(2)-dependent increase before shunt opening, but CO(2) reactivity was impaired after opening the shunt only in the MCA territory. This dog model features local hypoperfusion due to intracranial AV shunting and disturbance of CO(2) reactivity in the acute stage. The hemodynamics of this model will be confirmed in the chronic stage.

  18. Chagas disease as a cause of heart failure and ventricular arrhythmias in patients long removed from endemic areas: an emerging problem in Europe.

    Science.gov (United States)

    Vannucchi, Vieri; Tomberli, Benedetta; Zammarchi, Lorenzo; Fornaro, Alessandra; Castelli, Gabriele; Pieralli, Filippo; Berni, Andrea; Yacoub, Sophie; Bartoloni, Alessandro; Olivotto, Iacopo

    2015-12-01

    Chagas disease is a parasitic disease caused by the protozoan Trypanosoma cruzi. In endemic areas (South and Central America), Chagas disease represents a relevant public health issue, and is the most frequent cause of cardiomyopathy. In nonendemic areas, such as Europe, Chagas disease represents an emerging problem following the establishment of sizeable communities from Brazil and Bolivia. Chagas cardiomyopathy represents the most frequent and serious complication of chronic Chagas disease, affecting about 20-30% of patients, potentially leading to heart failure, arrhythmias, thromboembolism, stroke and sudden death. Because late complications of Chagas disease may develop several years or even decades after the acute infection, it may be extremely challenging to reach the correct diagnosis in patients long removed from the countries of origin. We report two examples of Chagas cardiomyopathy in South American women permanently residing in Italy for more than 20 years, presenting with cardiac manifestations ranging from left ventricular dysfunction and heart failure to isolated ventricular arrhythmias. The present review emphasizes that Chagas disease should be considered as a potential diagnosis in patients from endemic areas presenting with 'idiopathic' cardiac manifestations, even when long removed from their country of origin, with potential implications for treatment and control of Chagas disease transmission.

  19. Dobutamine Stress Echocardiography Safety in Chagas Disease Patients.

    Science.gov (United States)

    Rassi, Daniela do Carmo; Vieira, Marcelo Luiz Campos; Furtado, Rogerio Gomes; Turco, Fabio de Paula; Melato, Luciano Henrique; Hotta, Viviane Tiemi; Nunes, Colandy Godoy de Oliveira; Rassi, Luiz; Rassi, Salvador

    2017-02-01

    A few decades ago, patients with Chagas disease were predominantly rural workers, with a low risk profile for obstructive coronary artery disease (CAD). As urbanization has increased, they became exposed to the same risk factors for CAD of uninfected individuals. Dobutamine stress echocardiography (DSE) has proven to be an important tool in CAD diagnosis. Despite being a potentially arrhythmogenic method, it is safe for coronary patients without Chagas disease. For Chagas disease patients, however, the indication of DSE in clinical practice is uncertain, because of the arrhythmogenic potential of that heart disease. To assess DSE safety in Chagas disease patients with clinical suspicion of CAD, as well as the incidence of arrhythmias and adverse events during the exam. Retrospective analysis of a database of patients referred for DSE from May/2012 to February/2015. This study assessed 205 consecutive patients with Chagas disease suspected of having CAD. All of them had their serology for Chagas disease confirmed. Their mean age was 64±10 years and most patients were females (65.4%). No patient had significant adverse events, such as acute myocardial infarction, ventricular fibrillation, asystole, stroke, cardiac rupture and death. Regarding arrhythmias, ventricular extrasystoles occurred in 48% of patients, and non-sustained ventricular tachycardia in 7.3%. DSE proved to be safe in this population of Chagas disease patients, in which no potentially life-threatening outcome was found. Até poucas décadas atrás, os pacientes chagásicos eram predominantemente trabalhadores rurais, com baixo perfil de risco para doença obstrutiva coronária. Com a crescente urbanização, passaram a ter os mesmos fatores de risco para doença aterosclerótica que indivíduos não infectados. O ecocardiograma sob estresse com dobutamina (EED) é uma importante ferramenta no diagnóstico de coronariopatia. É referido, porém, como um método potencialmente arritmogênico, mas

  20. Dasatinib Reduces Lung Inflammation and Fibrosis in Acute Experimental Silicosis.

    Science.gov (United States)

    Cruz, Fernanda Ferreira; Horta, Lucas Felipe Bastos; Maia, Lígia de Albuquerque; Lopes-Pacheco, Miquéias; da Silva, André Benedito; Morales, Marcelo Marco; Gonçalves-de-Albuquerque, Cassiano Felippe; Takiya, Christina Maeda; de Castro-Faria-Neto, Hugo Caire; Rocco, Patricia Rieken Macedo

    2016-01-01

    Silicosis is an occupational lung disease with no effective treatment. We hypothesized that dasatinib, a tyrosine kinase inhibitor, might exhibit therapeutic efficacy in silica-induced pulmonary fibrosis. Silicosis was induced in C57BL/6 mice by a single intratracheal administration of silica particles, whereas the control group received saline. After 14 days, when the disease was already established, animals were randomly assigned to receive DMSO or dasatinib (1 mg/kg) by oral gavage, twice daily, for 14 days. On day 28, lung morphofunction, inflammation, and remodeling were investigated. RAW 264.7 cells (a macrophage cell line) were incubated with silica particles, followed by treatment or not with dasatinib, and evaluated for macrophage polarization. On day 28, dasatinib improved lung mechanics, increased M2 macrophage counts in lung parenchyma and granuloma, and was associated with reduction of fraction area of granuloma, fraction area of collapsed alveoli, protein levels of tumor necrosis factor-α, interleukin-1β, transforming growth factor-β, and reduced neutrophils, M1 macrophages, and collagen fiber content in lung tissue and granuloma in silicotic animals. Additionally, dasatinib reduced expression of iNOS and increased expression of arginase and metalloproteinase-9 in silicotic macrophages. Dasatinib was effective at inducing macrophage polarization toward the M2 phenotype and reducing lung inflammation and fibrosis, thus improving lung mechanics in a murine model of acute silicosis.

  1. Cannabinoid Receptor 2 Protects against Acute Experimental Sepsis in Mice

    Directory of Open Access Journals (Sweden)

    Huan Gui

    2013-01-01

    Full Text Available The systemic inflammatory response syndrome can be self-limited or can progress to severe sepsis and septic shock. Despite significant advances in the understanding of the molecular and cellular mechanisms of septic shock, it is still one of the most frequent and serious problems confronting clinicians in the treatments. And the effects of cannabinoid receptor 2 (CB2R on the sepsis still remain undefined. The present study was aimed to explore the role and mechanism of CB2R in acute sepsis model of mice. Here, we found that mice were more vulnerable for lipopolysaccharide- (LPS- induced death and inflammation after CB2R deletion (CB2R−/−. CB2R agonist, GW405833, could significantly extend the survival rate and decrease serum proinflammatory cytokines in LPS-treated mice. GW405833 dose-dependently inhibits proinflammatory cytokines release in splenocytes and peritoneal macrophages as well as splenocytes proliferation, and these effects were partly abolished in CB2R−/− splenocytes but completely abolished in CB2R−/− peritoneal macrophages. Further studies showed that GW405833 inhibits LPS-induced phosphorylation of ERK1/2 and STAT3 and blocks IκBα degradation and NF-κB p65 nuclear translocation in macrophages. All data together showed that CB2R provides a protection and is a potential therapeutic target for the sepsis.

  2. HEART ANEURYSM IN CHAGAS' DISEASE

    OpenAIRE

    OLIVEIRA,José Alberto Mello de

    1998-01-01

    This prospective study on 41 autopsy collected human hearts concerns the "apical" lesion in Chagas' disease. Previous report did not show a correlation between lesion frequency and heart weight then discarding a vascular factor in its pathogenesis. The present paper involves other variables besides the heart weight to evaluate the relative coronary insufficiency. Distinct colored gel (green and red) injected through the capillary beds of both coronary arteries defined the extent of both vesse...

  3. Opportunity cost for early treatment of Chagas disease in Mexico.

    Science.gov (United States)

    Ramsey, Janine M; Elizondo-Cano, Miguel; Sanchez-González, Gilberto; Peña-Nieves, Adriana; Figueroa-Lara, Alejandro

    2014-04-01

    Given current neglect for Chagas disease in public health programs in Mexico, future healthcare and economic development policies will need a more robust model to analyze costs and impacts of timely clinical attention of infected populations. A Markov decision model was constructed to simulate the natural history of a Chagas disease cohort in Mexico and to project the associated short and long-term clinical outcomes and corresponding costs. The lifetime cost for a timely diagnosed and treated Chagas disease patient is US$ 10,160, while the cost for an undiagnosed individual is US$ 11,877. The cost of a diagnosed and treated case increases 24-fold from early acute to indeterminate stage. The major cost component for lifetime cost was working days lost, between 44% and 75%, depending on the program scenario for timely diagnosis and treatment. In the long term, it is cheaper to diagnose and treat chagasic patients early, instead of doing nothing. This finding by itself argues for the need to shift current policy, in order to prioritize and attend this neglected disease for the benefit of social and economic development, which implies including treatment drugs in the national formularies. Present results are even more relevant, if one considers that timely diagnosis and treatment can arrest clinical progression and enhance a chronic patient's quality of life.

  4. Challenges in Chagas Disease Drug Discovery: A Review.

    Science.gov (United States)

    Paucar, Rocio; Moreno-Viguri, Elsa; Pérez-Silanes, Silvia

    2016-01-01

    Chagas disease or American trypanosomiasis is a neglected tropical disease caused by the parasite Trypanosoma cruzi. Although the number of infected individuals has decreased, about 6-7 million people are infected worldwide. The chemotherapy drugs currently used are limited to benznidazole and nifurtimox. They are effective in acute phase, congenital transmission and children with chronic infection; however, recent clinical trials have shown limitations in adults with chronic infection, presenting drawbacks during the treatment. Thus, there is an urgent need for new effective, safe and affordable drugs to fight against this complex disease. There were high expectations for azole derivatives as they appeared to be the most promising drugs for the treatment of Chagas disease during the last decade; however, the disappointing results obtained so far in clinical trials evidenced the lack of correlation between preclinical and clinical development. Therefore, the feedback obtained from these studies should define the starting point for addressing a roadmap for the drug discovery process in the fight against this disease. To tackle this challenge, it is important to keep in mind the drug target profile, already defined by panels of experts, and the coordinated work involving multi-disciplinary networks focusing not only on the discovery of new drugs but also on the standardization of the protocols that would allow acceleration in the Chagas disease drug discovery process.

  5. Novel cruzipain inhibitors for the chemotherapy of chronic Chagas disease.

    Science.gov (United States)

    Sbaraglini, María L; Bellera, Carolina L; Fraccaroli, Laura; Larocca, Luciana; Carrillo, Carolina; Talevi, Alan; Alba Soto, Catalina D

    2016-07-01

    Despite current efforts worldwide to develop new medications against Chagas disease, only two drugs are available, nifurtimox and benznidazole. Both drugs require prolonged treatment and have multiple side effects and limited efficacy on adult patients chronically infected with Trypanosoma cruzi. Recently, computer-guided drug repositioning led to the discovery of the trypanocidal effects of clofazimine and benidipine. These compounds showed inhibitory effects on cruzipain, the major cysteine protease of T. cruzi, of different parasite stages and in a murine model of acute Chagas disease. The aim of this work was to determine the efficacy of these novel cruzipain inhibitors when administered in a murine model of chronic Chagas disease. Benidipine and clofazimine were able to reduce the parasite burden in cardiac and skeletal muscles of chronically infected mice compared with untreated mice as well as diminish the inflammatory process in these tissues. Further studies should be performed to study the synergism with benznidazole and nifurtimox in view of combined therapies. Copyright © 2016 Elsevier B.V. and International Society of Chemotherapy. All rights reserved.

  6. Opportunity cost for early treatment of Chagas disease in Mexico.

    Directory of Open Access Journals (Sweden)

    Janine M Ramsey

    2014-04-01

    Full Text Available BACKGROUND: Given current neglect for Chagas disease in public health programs in Mexico, future healthcare and economic development policies will need a more robust model to analyze costs and impacts of timely clinical attention of infected populations. METHODOLOGY/PRINCIPAL FINDINGS: A Markov decision model was constructed to simulate the natural history of a Chagas disease cohort in Mexico and to project the associated short and long-term clinical outcomes and corresponding costs. The lifetime cost for a timely diagnosed and treated Chagas disease patient is US$ 10,160, while the cost for an undiagnosed individual is US$ 11,877. The cost of a diagnosed and treated case increases 24-fold from early acute to indeterminate stage. The major cost component for lifetime cost was working days lost, between 44% and 75%, depending on the program scenario for timely diagnosis and treatment. CONCLUSIONS/SIGNIFICANCE: In the long term, it is cheaper to diagnose and treat chagasic patients early, instead of doing nothing. This finding by itself argues for the need to shift current policy, in order to prioritize and attend this neglected disease for the benefit of social and economic development, which implies including treatment drugs in the national formularies. Present results are even more relevant, if one considers that timely diagnosis and treatment can arrest clinical progression and enhance a chronic patient's quality of life.

  7. Enfermedad de Chagas en Nicaragua

    Directory of Open Access Journals (Sweden)

    Carlos N. Talavera - López

    2008-04-01

    Full Text Available LA ENFERMEDAD DE CHAGAS ES UN PROBLEMA DE SALUD pública en toda Latinoamérica; alrededor de 20 millones de personas están infectadas y 200 millones están en riesgo de contraer la enfermedad. En 2006, la prevalencia en Centroamérica era del 7%. Actualmente no existe vacuna contra el protozoo y el tratamiento disponible resulta, aparte de poco efectivo, muy tóxico para el paciente. Los programas de control de vectores han ayudado a reducir los índices de infestación en Latinoamérica, pero aún falta mucho por hacer. En Nicaragua, la enfermedad de Chagas está subvalorada y los trabajos publicados son muy pocos. Es necesario investigar sobre esta enfermedad en nuestro país con otro enfoque, uno que no subvalore la enfermedad y ayude a desarrollar métodos diagnósticos y posibles tratamientos. Este artículo recopila información sobre los trabajos realizados porlos grupos más importantes de investigación en Chagas de Nicaragua en cuanto a epidemiología, control vectorial, diagnóstico y caracterización molecular.

  8. Molecular mechanisms of cardiac electromechanical remodeling during Chagas disease: Role of TNF and TGF-β.

    Science.gov (United States)

    Cruz, Jader Santos; Machado, Fabiana Simão; Ropert, Catherine; Roman-Campos, Danilo

    2017-02-01

    Chagas disease is caused by the trypanosomatid Trypanosoma cruzi, which chronically causes heart problems in up to 30% of infected patients. Chagas disease was initially restricted to Latin America. However, due to migratory events, this disease may become a serious worldwide health problem. During Chagas disease, many patients die of cardiac arrhythmia despite the apparent benefits of anti-arrhythmic therapy (e.g., amiodarone). Here, we assimilate the cardiac form of Chagas disease to an inflammatory cardiac disease. Evidence from the literature, mostly provided using experimental models, supports this view and argues in favor of new strategies for treating cardiac arrhythmias in Chagas disease by modulating cytokine production and/or action. But the complex nature of myocardial inflammation underlies the need to better understand the molecular mechanisms of the inflammatory response during Chagas disease. Here, particular attention has been paid to tumor necrosis factor alpha (TNF) and transforming growth factor beta (TGF-β) although other cytokines may be involved in the chagasic cardiomyopathy. Copyright © 2016 Elsevier Inc. All rights reserved.

  9. Aortic distensibility measured by pulse-wave velocity is not modified in patients with Chagas' disease

    Directory of Open Access Journals (Sweden)

    Arteaga Edmundo

    2006-06-01

    Full Text Available Abstract Background Experimental studies demonstrate that infection with trypanosoma cruzi causes vasculitis. The inflammatory lesion process could hypothetically lead to decreased distensibility of large and small arteries in advanced Chagas' disease. We tested this hypothesis. Methods and results We evaluated carotid-femoral pulse-wave velocity (PWV in 53 Chagas' disease patients compared with 31 healthy volunteers (control group. The 53 patients were classified into 3 groups: 1 16 with indeterminate form of Chagas' disease; 2 18 with Chagas' disease, electrocardiographic abnormalities, and normal systolic function; 3 19 with Chagas' disease, systolic dysfunction, and mild-to-moderate congestive heart failure. No difference was noted between the 4 groups regarding carotid-femoral PWV (8.4 ± 1.1 vs 8.2 ± 1.5 vs 8.2 ± 1.4 vs 8.7 ± 1.6 m/s, P = 0.6 or pulse pressure (39.5 ± 7.6 vs 39.3 ± 8.1 vs 39.5 ± 7.4 vs 39.7 ± 6.9 mm Hg, P = 0.9. A positive, significant, similar correlation occurred between PWV and age in patients with Chagas' disease (r = 0.42, P = 0.002, in controls (r = 0.48, P = 0.006, and also between PWV and systolic blood pressure in both groups (patients with Chagas' disease, r = 0.38, P = 0.005; healthy subjects, r = 0.36, P = 0.043. Conclusion Carotid femoral pulse-wave velocity is not modified in patients with Chagas' disease, suggesting that elastic properties of large arteries are not affected in this disorder.

  10. Clínica e terapêutica da doença de Chagas

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    Francisco S. Laranja

    1948-06-01

    ventriculares, bloqueio de ramo direito, bloqueios A-V de todos os graus e altrações atípicas do complexo ventricular são os achados eletrocardiográficos mais importantes. O bloqueio de ramo direito é excepcionalmente comum neste tipo de cardiopatia e possúe grande valor diagnóstico em areas endêmicas. Os critérios para o diagnóstico diferencial com outros tipos de cardiopatia crônica são expostos. A evolução da cardiopatia crônica é variável, dependendo principalmente da atividade da infecção. A sobrevida é geralmente longa; entretanto, a maioria dos doentes morre antes dos 50 anos de idade. O prognóstico depende principalmente de gráu de aumento do coração e de redução da sua capacidade funcional, do tipo de arritmia presente e do potencial evolutivo da infecção crônica. A morte súbita é muito comum nesta cardiopatia; a maioria dos doentes, porém, morre em insuficiencia cardiaca. Não se dispõe ainda de medicamento eficaz para o tratamento etiológico da doença de Chagas. No tratamento da insuficiência cardíaca da cardiopatia crônica da doença de Chagas obtém-se frequentemente melhores resultados com a estrofantina ou a ouabaina do que com a digital.1 - Based on the experience acquired in the last five years in Bambui, Minas Gerais, where more than six hundred cases of Chagas' disease have been studied, the authors have made a review of the clinical manifestations of this disease. Data on the incidence of schizotrypanosis are reported and the social importance of the disease, which is now being gradually, recognized, is stressed. 2 - The following classification of the clinical forms of the disease is suggested: a Acute form; b Chronic forms: 1 - Chronic indeterminate form 9potencial heart disease. 2- Chronic cardiac form (chronic Chagas' heart disease. No nervous manifestations of the kind of those described as the chronic nervous form of schizotrypanosis have been observed in the cases studied in Bambuí. 3 - Clinical and experimental

  11. Chagas disease risk in Texas.

    Science.gov (United States)

    Sarkar, Sahotra; Strutz, Stavana E; Frank, David M; Rivaldi, Chissa-Louise; Sissel, Blake; Sánchez-Cordero, Victor

    2010-10-05

    Chagas disease, caused by Trypanosoma cruzi, remains a serious public health concern in many areas of Latin America, including México. It is also endemic in Texas with an autochthonous canine cycle, abundant vectors (Triatoma species) in many counties, and established domestic and peridomestic cycles which make competent reservoirs available throughout the state. Yet, Chagas disease is not reportable in Texas, blood donor screening is not mandatory, and the serological profiles of human and canine populations remain unknown. The purpose of this analysis was to provide a formal risk assessment, including risk maps, which recommends the removal of these lacunae. The spatial relative risk of the establishment of autochthonous Chagas disease cycles in Texas was assessed using a five-stage analysis. 1. Ecological risk for Chagas disease was established at a fine spatial resolution using a maximum entropy algorithm that takes as input occurrence points of vectors and environmental layers. The analysis was restricted to triatomine vector species for which new data were generated through field collection and through collation of post-1960 museum records in both México and the United States with sufficiently low georeferenced error to be admissible given the spatial resolution of the analysis (1 arc-minute). The new data extended the distribution of vector species to 10 new Texas counties. The models predicted that Triatoma gerstaeckeri has a large region of contiguous suitable habitat in the southern United States and México, T. lecticularia has a diffuse suitable habitat distribution along both coasts of the same region, and T. sanguisuga has a disjoint suitable habitat distribution along the coasts of the United States. The ecological risk is highest in south Texas. 2. Incidence-based relative risk was computed at the county level using the Bayesian Besag-York-Mollié model and post-1960 T. cruzi incidence data. This risk is concentrated in south Texas. 3. The

  12. Chagas disease risk in Texas.

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    Sahotra Sarkar

    Full Text Available BACKGROUND: Chagas disease, caused by Trypanosoma cruzi, remains a serious public health concern in many areas of Latin America, including México. It is also endemic in Texas with an autochthonous canine cycle, abundant vectors (Triatoma species in many counties, and established domestic and peridomestic cycles which make competent reservoirs available throughout the state. Yet, Chagas disease is not reportable in Texas, blood donor screening is not mandatory, and the serological profiles of human and canine populations remain unknown. The purpose of this analysis was to provide a formal risk assessment, including risk maps, which recommends the removal of these lacunae. METHODS AND FINDINGS: The spatial relative risk of the establishment of autochthonous Chagas disease cycles in Texas was assessed using a five-stage analysis. 1. Ecological risk for Chagas disease was established at a fine spatial resolution using a maximum entropy algorithm that takes as input occurrence points of vectors and environmental layers. The analysis was restricted to triatomine vector species for which new data were generated through field collection and through collation of post-1960 museum records in both México and the United States with sufficiently low georeferenced error to be admissible given the spatial resolution of the analysis (1 arc-minute. The new data extended the distribution of vector species to 10 new Texas counties. The models predicted that Triatoma gerstaeckeri has a large region of contiguous suitable habitat in the southern United States and México, T. lecticularia has a diffuse suitable habitat distribution along both coasts of the same region, and T. sanguisuga has a disjoint suitable habitat distribution along the coasts of the United States. The ecological risk is highest in south Texas. 2. Incidence-based relative risk was computed at the county level using the Bayesian Besag-York-Mollié model and post-1960 T. cruzi incidence data. This

  13. Fase aguda da doença de Chagas na Amazônia brasileira: estudo de 233 casos do Pará, Amapá e Maranhão observados entre 1988 e 2005 Acute phase of Chagas disease in the Brazilian Amazon region: study of 233 cases from Pará, Amapá and Maranhão observed between 1988 and 2005

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    Ana Yecê das Neves Pinto

    2008-12-01

    Full Text Available Foram estudados 233 casos de fase aguda da doença de Chagas, oriundos do Pará, Amapá e Maranhão, observados no período de 1988 a 2005, cento e sessenta deles retrospectivamente de 1988 a 2002 e setenta e três prospectivamente de 2003 a 2005. Entre os casos estudados 78,5% (183/233 faziam parte de surtos provavelmente por transmissão oral, acometendo em média 4 pessoas e 21,5% (50/233 eram casos isolados. Foram considerados casos agudos aqueles que apresentaram exames parasitológicos diretos (a fresco, gota espessa ou Quantitative Buffy Coat - QBC e/ou IgM anti-Trypanosoma cruzi positivos. Foram feitos ainda xenodiagnósticos em 224 pacientes e hemoculturas em 213. Todos foram avaliados clinica e epidemiologicamente. As manifestações clínicas mais freqüentes foram febre (100%, cefaléia (92,3%, mialgia (84,1%, palidez (67%, dispnéia (58,4%, edema de membros inferiores (57,9%, edema de face (57,5% dor abdominal (44,2%, miocardite (39,9% e exantema (27%. O eletrocardiograma mostrou alterações de repolarização ventricular em 38,5% dos casos, baixa voltagem de QRS em 15,4% e desvio de SAQRS em 11,5%, extra-sístoles ventriculares em 5,8%, bradicardia em 5,8% e taquicardia em 5,8%, bloqueio de ramo direito em 4,8% e fibrilação atrial em 4,8%. A alteração mais freqüente vista no ecocardiograma foi o derrame pericárdico em 46,2% dos casos. Treze (5,6% pacientes evoluíram para o óbito, 10 (76,9% dos quais por comprometimento cardiovascular, dois por complicações de origem digestiva e um de causa mal definida.Two hundred and thirty-three cases of the acute phase of Chagas disease, from Pará, Amapá and Maranhão, were observed between 1988 and 2005. One hundred and sixty were studied retrospectively from 1988 to 2002 and seventy-three were prospectively followed up from 2003 to 2005. Among the cases studied, 78.5% (183/233 formed part of outbreaks, probably due to oral transmission (affecting a mean of 4 individuals, and 21

  14. Histopathologic identification of Trypanosoma cruzi (Chagas' encephalitis in an AIDS patient

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    Dimath Alyemni

    2017-03-01

    Full Text Available Trypanosoma cruzi (Chagas' encephalitis is an uncommon manifestation of T. cruzi infection, typically seen in immunocompromised patients. Encephalitis results from the reactivation of chronic infection predominately in individuals from endemic areas. Increased awareness of this complication is essential especially with increased migration of patients from endemic areas with concomitant HIV infection. Here we report a case of Chagas' encephalitis in an AIDS patient from Mexico in which there was no evidence of acute serologic, CSF, or blood infection by T. cruzi trypomastigotes.

  15. Papel do óxido nítrico no desenvolvimento de lesões cardíacas na fase aguda da infecção experimental pelo Trypanosoma cruzi Role of nitric oxide in the development of cardiac lesions during the acute phase of experimental infection by Trypanosoma cruzi

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    Cláudia Renata Bibiano Borges

    2009-04-01

    Full Text Available A doença de Chagas é causada pelo Trypanosoma cruzi e o coração é o órgão mais acometido. O óxido nítrico apresenta importante ação anti-Trypanosoma, porém, com pouca evidência de seu papel no mecanismo de lesão tecidual. O objetivo deste estudo foi analisar a contribuição do óxido nítrico no desenvolvimento da inflamação e da fibrose cardíaca na fase aguda da infecção experimental por cepas Y e Colombiana do Trypanosoma cruzi. A inflamação foi significativamente maior nos animais infectados pela cepa Colombiana, comparada com os infectados com a cepa Y, tanto nos animais C57BL/6 (3,98x1,87%; p=0,004 quanto nos animais C57BL/6 deficientes na sintase do óxido nítrico induzível (3,99x2,4%; p=0,013. O parasitismo cardíaco dos animais C57BL/6 deficientes na sintase do óxido nítrico induzível infectados pela cepa Colombiana foi significativamente maior que o destes mesmos animais infectados com a cepa Y (2,78x0,17 ninhos/mm²; p=0,004 assim como, os animais C57BL/6 infectados com a cepa Colombiana (2,78x1,33 ninhos/mm²; p=0,006 ou cepa Y (2,78x0,53 ninhos/mm²; p=0,005. Os dados reforçam o papel do óxido nítrico no controle do parasitismo e sugerem seu papel na proteção tecidual, controlando a inflamação e potencialmente diminuindo lesões cardíacas durante a fase aguda na doença de Chagas experimental.Chagas disease is caused by Trypanosoma cruzi and the heart is the organ most affected. Nitric oxide has notable anti-Trypanosoma action, but with little evidence regarding its role in the mechanism for tissue injury. The objective of this study was to analyze the contribution of nitric oxide towards the development of inflammation and cardiac fibrosis during the acute phase of experimental infection by Y and Colombian strains of Trypanosoma cruzi. The inflammation was significantly more intense in animals infected with the Colombian strain, compared with those infected with the Y strain, both in C57BL/6

  16. Does nitric oxide protect from microcirculatory disturbances in experimental acute pancreatitis in rats?

    Science.gov (United States)

    Dobosz, M; Hać, S; Wajda, Z

    1996-01-01

    The aim of the study was to investigate the potential role of nitric oxide (NO) on the microcirculation in experimental acute pancreatitis in rats. Twenty-five rats were divided into the following groups: group A (5 rats) = control; group B (5 rats) = acute pancreatitis induced by retrograde taurocholate infusion into the pancreatobiliary duct without treatment; group C (5 rats) = acute pancreatitis treated with the NO donor L-arginine; group D (5 rats) = acute pancreatitis treated with the NO synthase inhibitor N-nitro-L-arginine (L-NNA); group E (5 rats) = without pancreatitis receiving L-NNA. The animals were observed throughout 4 h. The microcirculatory values of the pancreas, liver, colon, stomach and kidney were measured by means of laser Doppler flowmetry. Three animals of group D died after the third hour of the experiment. In rats with pancreatitis, a rapid decrease in microcirculatory values was observed. The most pronounced drop in capillary blood flow within all the organs was observed in rats treated with the NO synthase inhibitor L-NNA, L-arginine administration in rats with acute pancreatitis slightly improved the microcirculatory values, although the improvement was significant in colon perfusion only. We conclude that NO may have a beneficial influence on the capillary organ perfusion in acute pancreatitis. The administration of an NO synthase inhibitor seems to have a detrimental effect on acute pancreatitis.

  17. Protein C activation during the initial phase of experimental acute pancreatitis in the rabbit

    DEFF Research Database (Denmark)

    Ottesen, L H; Bladbjerg, E-M; Osman, M

    2000-01-01

    BACKGROUND: Disturbances of coagulation and fibrinolysis are well-known systemic effects of acute necrotising pancreatitis (ANP). The purpose of this experimental study was to evaluate the initial events in the haemostatic activation during ANP in an animal model with relevance to the human situa...

  18. Rapid diagnostic tests duo as alternative to conventional serological assays for conclusive Chagas disease diagnosis.

    Science.gov (United States)

    Egüez, Karina E; Alonso-Padilla, Julio; Terán, Carolina; Chipana, Zenobia; García, Wilson; Torrico, Faustino; Gascon, Joaquim; Lozano-Beltran, Daniel-Franz; Pinazo, María-Jesús

    2017-04-01

    Chagas disease is caused by the parasite Trypanosoma cruzi. It affects several million people, mainly in Latin America, and severe cardiac and/or digestive complications occur in ~30% of the chronically infected patients. Disease acute stage is mostly asymptomatic and infection goes undiagnosed. In the chronic phase direct parasite detection is hampered due to its concealed presence and diagnosis is achieved by serological methods, like ELISA or indirect hemagglutination assays. Agreement in at least two tests must be obtained due to parasite wide antigenic variability. These techniques require equipped labs and trained personnel and are not available in distant regions. As a result, many infected people often remain undiagnosed until it is too late, as the two available chemotherapies show diminished efficacy in the advanced chronic stage. Easy-to-use rapid diagnostic tests have been developed to be implemented in remote areas as an alternative to conventional tests. They do not need electricity, nor cold chain, they can return results within an hour and some even work with whole blood as sample, like Chagas Stat-Pak (ChemBio Inc.) and Chagas Detect Plus (InBIOS Inc.). Nonetheless, in order to qualify a rapidly diagnosed positive patient for treatment, conventional serological confirmation is obligatory, which might risk its start. In this study two rapid tests based on distinct antigen sets were used in parallel as a way to obtain a fast and conclusive Chagas disease diagnosis using whole blood samples. Chagas Stat-Pak and Chagas Detect Plus were validated by comparison with three conventional tests yielding 100% sensitivity and 99.3% specificity over 342 patients seeking Chagas disease diagnosis in a reference centre in Sucre (Bolivia). Combined used of RDTs in distant regions could substitute laborious conventional serology, allowing immediate treatment and favouring better adhesion to it.

  19. Effects of melatonin in experimental stroke models in acute, sub-acute, and chronic stages

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    Hsiao-Wen Lin

    2009-03-01

    Full Text Available Hsiao-Wen Lin, E-Jian LeeNeurophysiology Laboratory, Neurosurgical Service, Department of Surgery, National Cheng Kung University Medical Center and Medical School, Tainan, TaiwanAbstract: Melatonin (N-acetyl-5-methoxy-tryptamine, a naturally occurring indole produced mainly by the pineal gland, is a well known antioxidant. Stroke (cerebral ischemia is the second leading cause of death worldwide. To date, however, effective and safe treatment for stroke remains unavailable. Melatonin is both lipid- and water-soluble and readily crosses the blood–brain barrier (BBB. Increasing evidence has shown that, in animal stroke models, administering melatonin significantly reduces infarct volume, edema, and oxidative damage and improves electrophysiological and behavioral performance. Here, we reviewed studies that assess effects of melatonin on cerebral ischemia in acute, sub-acute, and chronic stages. In addition to its potent antioxidant properties, melatonin exerts antiapoptotic, antiexcitotoxic, anti-inflammatory effects and promotes mitochondrial functions in animals with cerebral ischemia. Given that melatonin shows almost no toxicity to humans and possesses multifaceted protective capacity against cerebral ischemia, it is valuable to consider using melatonin in clinical trials on patients suffering from stroke.Keywords: cerebral ischemia, melatonin, stroke, neuroprotection

  20. Drugs for the Etiologic Treatment of Chagas Disease: Myths and Truths

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    Cynthia V. Rivero

    2016-01-01

    Full Text Available Chagas disease is a life-threatening illness caused by the protozoan parasite Trypanosoma cruzi. One of the characteristics of chronic chagasic infection is the parasitic persistence in cardiac and smooth muscle tissues. For this reason etiologic treatment of Chagas disease in all phases of infection is highly recommended. Despite the high number of trypanocidal drugs that have been discovered in the last years, only two compounds, Benznidazole and Nifurtimox remain as the unique drugs approved for Chagas treatment. Far from ideal, these drugs display low sensitivity and specificity resulting in limited applications, mainly in the onset of the acute phase. Thus there is an urgent need to validate new anti- T. cruzi drugs that can be applied even in the cases of chronic patients, those who today have no safe and effective treatment available. This paper reviews the most important compounds that have been tested in clinical trials and the results obtained to date.

  1. Towards a Paradigm Shift in the Treatment of Chronic Chagas Disease

    Science.gov (United States)

    Alarcón de Noya, B.; Araujo-Jorge, T.; Grijalva, M. J.; Guhl, F.; López, M. C.; Ramsey, J. M.; Ribeiro, I.; Schijman, A. G.; Sosa-Estani, S.; Torrico, F.; Gascon, J.

    2014-01-01

    Treatment for Chagas disease with currently available medications is recommended universally only for acute cases (all ages) and for children up to 14 years old. The World Health Organization, however, also recommends specific antiparasite treatment for all chronic-phase Trypanosoma cruzi-infected individuals, even though in current medical practice this remains controversial, and most physicians only prescribe palliative treatment for adult Chagas patients with dilated cardiomyopathy. The present opinion, prepared by members of the NHEPACHA network (Nuevas Herramientas para el Diagnóstico y la Evaluación del Paciente con Enfermedad de Chagas/New Tools for the Diagnosis and Evaluation of Chagas Disease Patients), reviews the paradigm shift based on clinical and immunological evidence and argues in favor of antiparasitic treatment for all chronic patients. We review the tools needed to monitor therapeutic efficacy and the potential criteria for evaluation of treatment efficacy beyond parasitological cure. Etiological treatment should now be mandatory for all adult chronic Chagas disease patients. PMID:24247135

  2. The porcine acute phase protein response to acute clinical and subclinical experimental infection with Streptococcus suis

    DEFF Research Database (Denmark)

    Sørensen, Nanna Skall; Tegtmeier, C.; Andresen, Lars Ole

    2006-01-01

    .i.), until the pigs were killed and autopsied on day 14 p.i. Clinical signs (fever and lameness) were observed in four of the five inoculated pigs from day 2 p.i., and these pigs also had arthritic lesions at autopsy. CRP and SAA showed fast increases in serum concentrations, CRP being elevated from days 1...... signs and no arthritic lesions showed an APP response comparable to that of the other, clinically affected pigs. Thus, both acute clinical and subclinical S. suis infection could be revealed by the measurement of one or more of the APPs CRP, SAA, Hp, pig-MAP and Apo A-I. The combined measurement of two...

  3. Estudo experimental sobre o congelamento do plasma e implicações referentes à transmissão da doença de chagas em serviços de hemoterapia

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    Vicente Amato Neto

    1975-06-01

    Full Text Available Plasmas de indivíduos normais e de pacientes com a forma crônica da doença de Chagas foram, intencionalmente, contaminados com cepa muito virulenta do Trypanosoma cruzi e, a seguir, congelados a -20°C, durante seis e 24 horas, como também no decurso de três ,sete, 14 e 21 dias. Depois de descongelamento em temperatura ambiente, ocorreram exame microsc��pico a fresco em contraste de fase, cultivo em meio de Warren e inoculação em camundongos, com subseqüente análise histopatológica do coração. Através dessas pesquisas, a sobrevivência do flagelado ficou avaliada, tendo sido verificado que o congelamento por três e 24 horas não impediu a persistência do parasita infetante. Salientaram os Autores que a investigação que levaram a efeito procurou contribuir no sentido de prestar orientação quanto às transfusões de plasmas, em Serviços de Hemoterapia, convindo frisar que no Brasil elas são efetuadas com razoável freqüênêcia, mediante utilização de doadores acometidos pela doença de Chagas e com a convicção de que baixas temperaturas promovem segura esterilização.The plasmas of normal subjets and of patients with chronic Chagas' disease were intentionally contaminated with a very virulent strain of Trypanosoma cruzi. The specimens were frozen to -20°C during three and twenty-four hours and for three, seven, fourteen and twenty-one days. After the aliquots were warmed to ambient temperature, they were examined as a fresh smearunder contrast phase microscopy, cultivated in Warren’s medium and inoculated in mice for subsequent histopathological examination of the heart. The results indicated that freezing durlng three and twenty-four hours did not prevent survival of the infecting parasite. The purpose of the study was to contribute to the orientation of plasma transfusion in blood transfusion centers. Since plasma transfusion is commonplace in, this country, many times colleeted from infected donors with Chagas

  4. Ergosterol biosynthesis and drug development for Chagas disease

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    Julio A Urbina

    2009-07-01

    Full Text Available This article presents an overview of the currently available drugs nifurtimox (NFX and benznidazole (BZN used against Trypanosoma cruzi, the aetiological agent of Chagas disease; herein we discuss their limitations along with potential alternatives with a focus on ergosterol biosynthesis inhibitors (EBI. These compounds are currently the most advanced candidates for new anti-T. cruzi agents given that they block de novo production of 24-alkyl-sterols, which are essential for parasite survival and cannot be replaced by a host's own cholesterol. Among these compounds, new triazole derivatives that inhibit the parasite's C14± sterol demethylase are the most promising, as they have been shown to have curative activity in murine models of acute and chronic Chagas disease and are active against NFX and BZN-resistant T. cruzi strains; among this class of compounds, posaconazole (Schering-Plough Research Institute and ravuconazole (Eisai Company are poised for clinical trials in Chagas disease patients in the short term. Other T. cruzi-specific EBI, with in vitro and in vivo potency, include squalene synthase, lanosterol synthase and squalene epoxidase-inhibitors as well as compounds with dual mechanisms of action (ergosterol biosynthesis inhibition and free radical generation, but they are less advanced in their development process. The main putative advantages of EBI over currently available therapies include their higher potency and selectivity in both acute and chronic infections, activity against NFX and BZN-resistant T. cruzi strains, and much better tolerability and safety profiles. Limitations may include complexity and cost of manufacture of the new compounds. As for any new drug, such compounds will require extensive clinical testing before being introduced for clinical use, and the complexity of such studies, particularly in chronic patients, will be compounded by the current limitations in the verification of true parasitological cures for

  5. Vibratory sensory testing in acute compartment syndromes: a clinical and experimental study.

    Science.gov (United States)

    Phillips, J H; Mackinnon, S E; Beatty, S E; Dellon, A L; O'Brien, J P

    1987-05-01

    Invasive and noninvasive diagnostic testing was correlated in 11 patients with acute compartmental syndromes of the forearm. The excellent correlation between diminished perception of vibration and increasing compartmental pressure suggested that 256 cycle per second (cps) vibratory stimuli may be useful clinically in determining the appropriate time for surgical intervention in the acute compartmental syndrome. In 12 adult male volunteers, elevated compartment pressures were created in the anterior tibial compartment of the leg. A decrease in perception to 256 cycle per second (cps) vibratory stimulus was the earliest sensory abnormality to occur with elevated tissue compartment pressures. Analysis of variance showed significantly that 256-cps vibration was the most reliable and earliest sensory modality to change at pressures of 35 to 40 mmHg. These clinical and experimental findings support the use of the 256-cps tuning fork as a noninvasive diagnostic test in the evaluation of the patient with suspected acute compartment syndrome.

  6. Phased-array intracardiac echocardiographic imaging of acute cardiovascular emergencies: Experimental studies in dogs.

    Science.gov (United States)

    Yamada, Elina; Zhang, Yi; Davies, Ray; Coddington, William; Kerber, Richard E

    2002-10-01

    We evaluated a newly developed phased-array intracardiac echocardiographic catheter. Our aim was to evaluate the imaging capability of this new ICE catheter in an animal model simulating acute cardiovascular abnormalities. ICE images were obtained from the right atrium during (1) acute left ventricular dysfunction; (2) acute coronary occlusion; (3) pericardial effusion and tamponade; and (4) pulmonary embolism. Left ventricular dysfunction, induced experimentally by halothane inhalation, resulted in a fall in echocardiography-calculated ejection fraction from 47% +/- 11% to 25% +/- 10%, P small as 15 mL. Right ventricular and atrial compression and respiratory variation in right ventricular inflow during tamponade were demonstrated. After injection of intravenous thrombin to create venous thromboembolism, we demonstrated right ventricular dilatation and dysfunction and thrombi attached to the tricuspid and pulmonary valves and in the pulmonary artery. This new phased-array ICE catheter may be a useful clinical tool for the diagnosis of heart failure, ischemia, tamponade, and pulmonary embolism.

  7. Quantitative and qualitative leukocyte abnormalities in dogs with experimental and naturally occurring acute canine monocytic ehrlichiosis.

    Science.gov (United States)

    Gianopoulos, Athena; Mylonakis, Mathios E; Theodorou, Konstantina; Christopher, Mary M

    2016-06-01

    Canine monocytic ehrlichiosis (CME) is one of the most important tick-borne diseases worldwide. Cytopenias have been observed in both acute (nonmyelosuppressive) and chronic (myelosuppressive) CME; however, leukocyte abnormalities and indices have been incompletely described in dogs with acute CME. The aims of this study were to analyze temporal changes in differential leukocyte counts, leukocyte morphology, myeloperoxidase index (MPXI), and lobularity index (LI) in dogs with experimental and naturally occurring acute CME. Differential leukocyte counts and morphology were evaluated in archived blood smears from 13 Beagle dogs experimentally infected with Ehrlichia canis and evaluated weekly for 42 days postinfection (DPI); 20 dogs with naturally occurring acute CME also were evaluated. MPXI and LI were obtained from ADVIA reports. Wilcoxon tests were used to assess changes over time; leukogram results in natural cases were assessed in comparison with reference intervals. In experimental dogs, significant decreases in neutrophil, monocyte, lymphocyte, and eosinophil counts, and a mild left shift occurred within 14 DPI. The MPXI decreased significantly between 14 and 21 DPI and remained low, while LI increased from 14 to 35 DPI. Lymphocyte counts rebounded at 21 DPI, normalizing total WBC counts. Neutrophil toxicity was seen rarely, but reactive lymphocytes were observed frequently. Dogs with natural infection had variable patterns of leukocyte changes. Acute CME is associated with several discrete quantitative and qualitative leukogram changes indicative of concurrent inflammation, antigenic stimulation, and stress. Changes in MPXI and LI warrant further investigation in dogs with CME and other diseases. © 2016 American Society for Veterinary Clinical Pathology.

  8. Melatonin in Chagas´ disease: Possible therapeutic value

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    Daniel P. Cardinali

    2011-10-01

    Full Text Available Chagas' disease is a severe health problem in Latin America, causing approximately 50 000 deaths a year, with approximately 18 million infected people. About 25-30% of the patients infected with Trypanosoma cruzi develop the chronic form of the disease. The protective response against T. cruzi depends on both innate and acquired immunity involving macrophages, natural killer cells, T and B lymphocytes, and the production of proinflammatory Th-1 cytokines. In addition, an increased nitric oxide (NO production in macrophages leading to effective microbicidal action is needed to control parasitemia. Melatonin is detectable in T. cruzi and may play a role in promoting infection whereas, when administered in high doses during the acute phase of T. cruzi infection, it can decrease parasitemia while reducing NO production. During chronic disease progression, the sustained oxidative stress concomitant to myocardial damage could be reduced by administering melatonin. It is hypothesized that the coordinated administration of a melatonin agonist like the MT1/MT2 agonist ramelteon, that lacks antioxidant activity and may not affect NO production during the acute phase, and of melatonin in doses high enough to decrease oxidative damage, to preserve mitochondrial and to prevent cardiomyopathy during the chronic phase, could be a novel add-on treatment of Chagas´ disease.

  9. Experimental study of the diagnostic potentialities of bioimpedance measurement in acute intestinal obstruction.

    Science.gov (United States)

    Rodin, A V; Pleshkov, V G; Leonov, S D; Bazhenov, S M

    2013-10-01

    The dynamics of impedance values of the small and large intestine, parietal peritoneum, and greater omentum was analyzed during different periods of experimental acute intestinal obstruction. The impedance was below the normal, which indicated progressive microcirculatory disorders and necrosis of the intestinal wall. The histomorphological picture of healing of anastomoses created after resection of the intestine with consideration for bioimpedance values and of anastomoses created after resection of the intestine in a priori viable tissues virtually did not differ.

  10. Update on oral Chagas disease outbreaks in Venezuela: epidemiological, clinical and diagnostic approaches

    Science.gov (United States)

    de Noya, Belkisyolé Alarcón; Díaz-Bello, Zoraida; Colmenares, Cecilia; Ruiz-Guevara, Raiza; Mauriello, Luciano; Muñoz-Calderón, Arturo; Noya, Oscar

    2015-01-01

    Orally transmitted Chagas disease has become a matter of concern due to outbreaks reported in four Latin American countries. Although several mechanisms for orally transmitted Chagas disease transmission have been proposed, food and beverages contaminated with whole infected triatomines or their faeces, which contain metacyclic trypomastigotes of Trypanosoma cruzi, seems to be the primary vehicle. In 2007, the first recognised outbreak of orally transmitted Chagas disease occurred in Venezuela and largest recorded outbreak at that time. Since then, 10 outbreaks (four in Caracas) with 249 cases (73.5% children) and 4% mortality have occurred. The absence of contact with the vector and of traditional cutaneous and Romana’s signs, together with a florid spectrum of clinical manifestations during the acute phase, confuse the diagnosis of orally transmitted Chagas disease with other infectious diseases. The simultaneous detection of IgG and IgM by ELISA and the search for parasites in all individuals at risk have been valuable diagnostic tools for detecting acute cases. Follow-up studies regarding the microepidemics primarily affecting children has resulted in 70% infection persistence six years after anti-parasitic treatment. Panstrongylus geniculatus has been the incriminating vector in most cases. As a food-borne disease, this entity requires epidemiological, clinical, diagnostic and therapeutic approaches that differ from those approaches used for traditional direct or cutaneous vector transmission. PMID:25946155

  11. [Chagas disease in the Netherlands: an estimate of the number of patients].

    Science.gov (United States)

    Bart, Aldert; Hodiamont, Caspar J; Grobusch, Martin P; van den Brink, Reneé B A; Smout, André J P M; van Gool, Tom

    2011-01-01

    A total of 8-10 million persons are infected worldwide with Trypanosoma cruzi, the causative parasite of Chagas disease, most of whom are inhabitants of Latin America. Due to the increased migration of peoples, Chagas disease has been on the uprise outside Latin America, including in Europe. The course of Chagas, also called American trypanosomiasis, runs in 2 phases: an acute phase lasting approximately 2 months, and a chronic phase in which symptoms may appear years after infection. Without treatment, the patient will remain infected for life. The acute phase is usually asymptomatic; in the chronic phase of American trypanosomiasis, severe gastro-intestinal and cardiac abnormalities may develop, finally with fatal course. In the Netherlands, the number of immigrants who would serologically test positive for American trypanosomiasis is estimated to be between 726 and 2929. Healthcare providers in the Netherlands may encounter patients who have Chagas disease more and more frequently. The screening of pregnant women and blood donors at risk for American trypanosomiasis should be considered.

  12. [Experimental study of anatomo-pathological and physiopathological manifestations of acute cholecystitis].

    Science.gov (United States)

    Vayre, P; Delavierre, P; Duran, M

    1976-01-01

    From their experimental findings in 120 rabbits, the authors conclude that, at first, cholecystitis is usually an aseptic lesion and infection occurs only secondarily. In a large number of cases the initial physiopathological mechanism is that of inflammation which may be due to mechanical causes such as obstruction of the gall bladder siphon and vasomotor phenomena under autonomic control. The histological lesions and course are comparable to those observed in clinical medicine. The interest of this experimental study is to compare the pathology of acute cholecystitis with pancreatitis and Reilly's syndrome and Gregoire and Couvelaire's theory of visceral apoplexy.

  13. Chaga mushroom-induced oxalate nephropathy.

    Science.gov (United States)

    Kikuchi, Yuko; Seta, Koichi; Ogawa, Yayoi; Takayama, Tatsuya; Nagata, Masao; Taguchi, Takashi; Yahata, Kensei

    2014-06-01

    Chaga mushrooms have been used in folk and botanical medicine as a remedy for cancer, gastritis, ulcers, and tuberculosis of the bones. A 72-year-old Japanese female had been diagnosed with liver cancer 1 year prior to presenting at our department. She underwent hepatectomy of the left lobe 3 months later. Chaga mushroom powder (4 - 5 teaspoons per day) had been ingested for the past 6 months for liver cancer. Renal function decreased and hemodialysis was initiated. Renal biopsy specimens showed diffuse tubular atrophy and interstitial fibrosis. Oxalate crystals were detected in the tubular lumina and urinary sediment and oxalate nephropathy was diagnosed. Chaga mushrooms contain extremely high oxalate concentrations. This is the first report of a case of oxalate nephropathy associated with ingestion of Chaga mushrooms.

  14. [Brazilian Consensus on Chagas Disease, 2015].

    Science.gov (United States)

    Dias, João Carlos Pinto; Ramos, Alberto Novaes; Gontijo, Eliane Dias; Luquetti, Alejandro; Shikanai-Yasuda, Maria Aparecida; Coura, José Rodrigues; Torres, Rosália Morais; Melo, José Renan da Cunha; Almeida, Eros Antonio de; Oliveira, Wilson de; Silveira, Antônio Carlos; Rezende, Joffre Marcondes de; Pinto, Fabiane Scalabrini; Ferreira, Antonio Walter; Rassi, Anis; Fragata, Abílio Augusto; Sousa, Andréa Silvestre de; Correia, Dalmo; Jansen, Ana Maria; Andrade, Glaucia Manzan Queiroz; Britto, Constança Felícia De Paoli de Carvalho; Pinto, Ana Yecê das Neves; Rassi, Anis; Campos, Dayse Elisabeth; Abad-Franch, Fernando; Santos, Silvana Eloi; Chiari, Egler; Hasslocher-Moreno, Alejandro Marcel; Moreira, Eliane Furtado; Marques, Divina Seila de Oliveira; Silva, Eliane Lages; Marin-Neto, José Antonio; Galvão, Lúcia Maria da Cunha; Xavier, Sergio Salles; Valente, Sebastião Aldo da Silva; Carvalho, Noêmia Barbosa; Cardoso, Alessandra Viana; Silva, Rafaella Albuquerque E; Costa, Veruska Maia da; Vivaldini, Simone Monzani; Oliveira, Suelene Mamede; Valente, Vera da Costa; Lima, Mayara Maia; Alves, Renato Vieira

    2016-06-01

    Chagas disease is a neglected chronic condition that presents high morbidity and mortality burden, with considerable psychological, social, and economic impact. The disease represents a significant public health issue in Brazil, with different regional patterns. This document presents the evidence that resulted in the Brazilian Consensus on Chagas Disease. The objective was to review and standardize strategies for diagnosis, treatment, prevention, and control of Chagas disease in the country, based on the available scientific evidence. The consensus is based on collaboration and contribution of renowned Brazilian experts with vast knowledge and experience on various aspects of the disease. It is the result of close collaboration between the Brazilian Society of Tropical Medicine and the Ministry of Health. This document shall strengthen the development of integrated control measures against Chagas disease in the country, focusing on epidemiology, management, comprehensive care (including families and communities), communication, information, education, and research.

  15. Chagas Heart Disease: Report on Recent Developments

    Science.gov (United States)

    Machado, Fabiana S.; Jelicks, Linda A.; Kirchhoff, Louis V.; Shirani, Jamshid; Nagajyothi, Fnu; Mukherjee, Shankar; Nelson, Randin; Coyle, Christina M.; Spray, David C.; Campos de Carvalho, Antonio C.; Guan, Fangxia; Prado, Cibele M.; Lisanti, Michael P.; Weiss, Louis M.; Montgomery, Susan P.; Tanowitz, Herbert B.

    2011-01-01

    Chagas disease, caused by the parasite Trypanosoma cruzi, is an important cause of cardiac disease in endemic areas of Latin America. It is now being diagnosed in non-endemic areas due to immigration. Typical cardiac manifestations of Chagas disease include dilated cardiomyopathy, congestive heart failure, arrhythmias, cardioembolism and stroke. Clinical and laboratory-based research to define the pathology resulting from T. cruzi infection has shed light on many of the cellular and molecular mechanisms leading to these manifestations. Antiparasitic treatment may not be appropriate for patients with advanced cardiac disease. Clinical management of Chagas heart disease is similar to that used for cardiomyopathies due to other processes. Cardiac transplantation has been successfully performed in a small number of patients with Chagas heart disease. PMID:22293860

  16. Hepatic perfusion changes in an experimental model of acute pancreatitis: Evaluation by perfusion CT

    Energy Technology Data Exchange (ETDEWEB)

    Tutcu, Semra [Department of Surgery, Celal Bayar University, School of Medicine, Manisa (Turkey); Serter, Selim, E-mail: serterselim@gmail.co [Department of Radiology, Celal Bayar University, School of Medicine, Manisa (Turkey); Kaya, Yavuz; Kara, Eray [Department of Surgery, Celal Bayar University, School of Medicine, Manisa (Turkey); Nese, Nalan [Department of Pathology, Celal Bayar University, School of Medicine, Manisa (Turkey); Pekindil, Goekhan [Department of Radiology, Celal Bayar University, School of Medicine, Manisa (Turkey); Coskun, Teoman [Department of Surgery, Celal Bayar University, School of Medicine, Manisa (Turkey)

    2010-08-15

    Purpose: It is known that acute pancreatitis may cause secondary changes in several organs. Liver is one of these involved organs. In different experimental studies hepatic damages were shown histopathologically in acute pancreatitis but there are a few studies about perfusion disorders that accompany these histopathologic changes. Perfusion CT (pCT) provides the ability to detect regional and global alterations in organ blood flow. The purpose of the study was to describe hepatic perfusion changes in experimental acute pancreatitis model with pCT. Materials and methods: Forty Sprague-Dawley rats of both genders with average weights of 250 g were used. Rats were randomized into two groups. Twenty rats were in control group and 20 in acute pancreatitis group. pCT was performed. Perfusion maps were formed by processing the obtained images with perfusion CT software. Blood flow (BF) and blood volume (BV) values were obtained from these maps. All pancreatic and liver tissues were taken off with laparotomy and histopathologic investigation was performed. Student's t test was used for statistical analyses. Results: In pCT we found statistically significant increase in blood volume in both lobes of liver and in blood flow in right lobe of the liver (p < 0.01). Although blood flow in left lobe of the liver increased, it did not reach statistical significance. Conclusion: The quantitative analysis of liver parenchyma with pCT showed that acute pancreatitis causes a significant perfusion changes in the hepatic tissue. Systemic mediators seem to be effective as well as local inflammatory changes in perfusion changes.

  17. Evolution of the clinical and epidemiological knowledge about Chagas disease 90 years after its discovery

    Directory of Open Access Journals (Sweden)

    Prata Aluízio

    1999-01-01

    Full Text Available Three different periods may be considered in the evolution of knowledge about the clinical and epidemiological aspects of Chagas disease since its discovery: (a early period concerning the studies carried out by Carlos Chagas in Lassance with the collaboration of other investigators of the Manguinhos School. At that time the disease was described and the parasite, transmitters and reservoirs were studied. The coexistence of endemic goiter in the same region generated some confusion about the clinical forms of the disease; (b second period involving uncertainty and the description of isolated cases, which lasted until the 1940 decade. Many acute cases were described during this period and the disease was recognized in many Latin American countries. Particularly important were the studies of the Argentine Mission of Regional Pathology Studies, which culminated with the description of the Romaña sign in the 1930 decade, facilitating the diagnosis of the early phase of the disease. However, the chronic phase, which was the most important, continued to be difficult to recognize; (c period of consolidation of knowledge and recognition of the importance of Chagas disease. Studies conducted by Laranja, Dias and Nóbrega in Bambuí updated the description of Chagas heart disease made by Carlos Chagas and Eurico Villela. From then on, the disease was more easily recognized, especially with the emphasis on the use of a serologic diagnosis; (d period of enlargement of knowledges on the disease. The studies on denervation conducted in Ribeirão Preto by Fritz Köberle starting in the 1950 decade led to a better understanding of the relations between Chagas disease and megaesophagus and other visceral megas detected in endemic areas.

  18. Pathogenesis of chronic Chagas cardiomyopathy: the role of coronary microvascular derangements

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    Jose Antonio Marin-Neto

    2013-09-01

    Full Text Available There is ample experimental and clinical evidence of functional and structural microvascular abnormalities occurring in patients with Chagas cardiomyopathy, possibly due to the inflammatory process and/or autonomic disturbances caused by Trypanosoma cruzi infection. Those microvascular derangements are likely to constitute at least an ancillary factor that potentiates and amplifies the chronic inflammation in myocardial tissue. It is possible to devise appropriate therapeutic interventions aimed at reverting or slowing the progression of the microvascular abnormalities to positively affect the natural history of Chagas cardiomyopathy.

  19. Experimental american trypanomiasis in rats: sympathetic denervation, parasitism and inflammatory process Desnervação simpática, parasitismo e processo inflamatório durante a doença de Chagas experimental, em ratos

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    Conceição R. S. Machado

    1989-12-01

    Full Text Available Tissue parasitism, inflammatory process (histologic methods and sympathetic denervation (glyoxylic acid-induced histofluorescence for demonstration of catecholamines were studied in the heart (atrium and verntricle and the submandibular gland of rats infected with the Y strain of Trypanosoma cruzi. In the heart paralleling intense parasitism and inflammatory process, the sympathetic denervation started at day 6 of infection and at the end of the acute phase (day 20 practically no varicose nerve terminals were found in both myocardium and vessels. In the submandibular gland, in spite of the rarity of anastigote pseudocysts and the scarcity of inflammatory foci, slight to moderate (days 13-15 of infection or moderate to severe denervation (day 20 was found. At day 120 of infection both organs exhibited normal pattern of sympathetic innervation and only the heart showed some inflammatory foci and rare psudocysts (ventricle. Our data suggest the involvement of circulating factors in the sympathetic denervation phenomena but indicate that local inflammatory process is, at least, an aggravating factor.Parasitismo tecidual, processo inflamatório (métodos histológicos e desnervação simpática (histofluorescência induzida por ácido glioxílico para demosntração de catecolaminas foram estudados no coração (átrio e ventrículo e na glândula submandibular de ratos infectados com cepa Y de Trypanosoma cruzi. No coração, em paralelo com intenso parasitismo e processo inglamatório, a desnervação simpática iniciuo-se no 6º dia de infecção e ao fim da fase aguda (20º dia praticamente nenhuma terminação nervosa varicosa foi encontrada tanto no miocárdio como em vasos. Na glândula submandibular, apesar da raridade de ninhos de amastigotas e da escassez de focos inflamatórios, encontram-se discreta e moderada 13º-15º dia de infeccção ou moderada a severa (20º dia desnervação. Aos 120 dias de infecção, ambos os órgãos exibiram

  20. Resveratrol Reverses Functional Chagas Heart Disease in Mice

    Science.gov (United States)

    Mata-Santos, Hilton; Vicentino, Amanda R. R.; Feijó, Daniel F.; Meyer-Fernandes, José R.; Paula-Neto, Heitor A.; Medei, Emiliano; Bozza, Marcelo T.; Lannes-Vieira, Joseli; Paiva, Claudia N.

    2016-01-01

    Chronic chagasic cardiomyopathy (CCC) develops years after acute infection by Trypanosoma cruzi and does not improve after trypanocidal therapy, despite reduction of parasite burden. During disease, the heart undergoes oxidative stress, a potential causative factor for arrhythmias and contractile dysfunction. Here we tested whether antioxidants/ cardioprotective drugs could improve cardiac function in established Chagas heart disease. We chose a model that resembles B1-B2 stage of human CCC, treated mice with resveratrol and performed electrocardiography and echocardiography studies. Resveratrol reduced the prolonged PR and QTc intervals, increased heart rates and reversed sinus arrhythmia, atrial and atrioventricular conduction disorders; restored a normal left ventricular ejection fraction, improved stroke volume and cardiac output. Resveratrol activated the AMPK-pathway and reduced both ROS production and heart parasite burden, without interfering with vascularization or myocarditis intensity. Resveratrol was even capable of improving heart function of infected mice when treatment was started late after infection, while trypanocidal drug benznidazole failed. We attempted to mimic resveratrol’s actions using metformin (AMPK-activator) or tempol (SOD-mimetic). Metformin and tempol mimicked the beneficial effects of resveratrol on heart function and decreased lipid peroxidation, but did not alter parasite burden. These results indicate that AMPK activation and ROS neutralization are key strategies to induce tolerance to Chagas heart disease. Despite all tissue damage observed in established Chagas heart disease, we found that a physiological dysfunction can still be reversed by treatment with resveratrol, metformin and tempol, resulting in improved heart function and representing a starting point to develop innovative therapies in CCC. PMID:27788262

  1. Carlos Chagas Discoveries as a Drop Back to Scientific Construction of Chronic Chagas Heart Disease.

    Science.gov (United States)

    Bestetti, Reinaldo B; Restini, Carolina Baraldi A; Couto, Lucélio B

    2016-07-01

    The scientific construction of chronic Chagas heart disease (CCHD) started in 1910 when Carlos Chagas highlighted the presence of cardiac arrhythmia during physical examination of patients with chronic Chagas disease, and described a case of heart failure associated with myocardial inflammation and nests of parasites at autopsy. He described sudden cardiac death associated with arrhythmias in 1911, and its association with complete AV block detected by Jacquet's polygraph as Chagas reported in 1912. Chagas showed the presence of myocardial fibrosis underlying the clinical picture of CCHD in 1916, he presented a full characterization of the clinical aspects of CCHD in 1922. In 1928, Chagas detected fibrosis of the conductive system, and pointed out the presence of marked cardiomegaly at the chest X-Ray associated with minimal symptomatology. The use of serological reaction to diagnose CCHD was put into clinical practice in 1936, after Chagas' death, which along with the 12-lead ECG, revealed the epidemiological importance of CCHD in 1945. In 1953, the long period between initial infection and appearance of CCHD was established, whereas the annual incidence of CCHD from patients with the indeterminate form of the disease was established in 1956. The use of heart catheterization in 1965, exercise stress testing in 1973, Holter monitoring in 1975, Electrophysiologic testing in 1973, echocardiography in 1975, endomyocardial biopsy in 1981, and Magnetic Resonance Imaging in 1995, added to the fundamental clinical aspects of CCHD as described by Carlos Chagas.

  2. Carlos Chagas Discoveries as a Drop Back to Scientific Construction of Chronic Chagas Heart Disease

    Directory of Open Access Journals (Sweden)

    Reinaldo B. Bestetti

    2016-01-01

    Full Text Available Abstract The scientific construction of chronic Chagas heart disease (CCHD started in 1910 when Carlos Chagas highlighted the presence of cardiac arrhythmia during physical examination of patients with chronic Chagas disease, and described a case of heart failure associated with myocardial inflammation and nests of parasites at autopsy. He described sudden cardiac death associated with arrhythmias in 1911, and its association with complete AV block detected by Jacquet's polygraph as Chagas reported in 1912. Chagas showed the presence of myocardial fibrosis underlying the clinical picture of CCHD in 1916, he presented a full characterization of the clinical aspects of CCHD in 1922. In 1928, Chagas detected fibrosis of the conductive system, and pointed out the presence of marked cardiomegaly at the chest X-Ray associated with minimal symptomatology. The use of serological reaction to diagnose CCHD was put into clinical practice in 1936, after Chagas' death, which along with the 12-lead ECG, revealed the epidemiological importance of CCHD in 1945. In 1953, the long period between initial infection and appearance of CCHD was established, whereas the annual incidence of CCHD from patients with the indeterminate form of the disease was established in 1956. The use of heart catheterization in 1965, exercise stress testing in 1973, Holter monitoring in 1975, Electrophysiologic testing in 1973, echocardiography in 1975, endomyocardial biopsy in 1981, and Magnetic Resonance Imaging in 1995, added to the fundamental clinical aspects of CCHD as described by Carlos Chagas.

  3. Carlos Chagas Discoveries as a Drop Back to Scientific Construction of Chronic Chagas Heart Disease

    Energy Technology Data Exchange (ETDEWEB)

    Bestetti, Reinaldo B., E-mail: rbestetti44@gmail.com; Restini, Carolina Baraldi A.; Couto, Lucélio B. [Universidade de Ribeirão Preto, Ribeirão Preto, São Paulo, SP (Brazil)

    2016-07-15

    The scientific construction of chronic Chagas heart disease (CCHD) started in 1910 when Carlos Chagas highlighted the presence of cardiac arrhythmia during physical examination of patients with chronic Chagas disease, and described a case of heart failure associated with myocardial inflammation and nests of parasites at autopsy. He described sudden cardiac death associated with arrhythmias in 1911, and its association with complete AV block detected by Jacquet's polygraph as Chagas reported in 1912. Chagas showed the presence of myocardial fibrosis underlying the clinical picture of CCHD in 1916, he presented a full characterization of the clinical aspects of CCHD in 1922. In 1928, Chagas detected fibrosis of the conductive system, and pointed out the presence of marked cardiomegaly at the chest X-Ray associated with minimal symptomatology. The use of serological reaction to diagnose CCHD was put into clinical practice in 1936, after Chagas' death, which along with the 12-lead ECG, revealed the epidemiological importance of CCHD in 1945. In 1953, the long period between initial infection and appearance of CCHD was established, whereas the annual incidence of CCHD from patients with the indeterminate form of the disease was established in 1956. The use of heart catheterization in 1965, exercise stress testing in 1973, Holter monitoring in 1975, Electrophysiologic testing in 1973, echocardiography in 1975, endomyocardial biopsy in 1981, and Magnetic Resonance Imaging in 1995, added to the fundamental clinical aspects of CCHD as described by Carlos Chagas.

  4. [Resveratrol improves coronary collateral circulation in pigs with experimental acute coronary occlusion].

    Science.gov (United States)

    Wang, Zhi-rong; Xu, Wu; Zhang, Chao-qun; Xie, Wei; Zhou, Zhao-feng; Zhou, Xiao-feng; Zhang, Zhuo-qi

    2011-10-01

    To evaluate the impact of resveratrol on coronary collateral circulation in pigs suffered from experimental acute coronary occlusion. Eighteen healthy pigs were randomly divided into 3 groups: resveratrol group, nitroglycerin group and control group. Animal model of acute coronary occlusion was established through PTCA method, and the blood flow spectrum in the left circumflex artery (LCX) was detected using intracoronary Doppler ultrasound. The average peak velocity (APV) in infarction correlation artery (IRA) was significantly decreased immediately after coronary occlusion [(0.85 ± 0.25) cm/s vs. (24.83 ± 3.43) cm/s, P coronary injection of resveratrol (2 mg) or nitroglycerin (0.3 mg). There was no significant difference in peak APV between the resveratrol and nitroglycerin groups. The duration of increased APV was significantly longer in resveratrol group than that in nitroglycerin group [(58.83 ± 6.15) min vs. (21.80 ± 5.79) min, P circulation after acute coronary occlusion was obviously insufficient in pigs. Resveratrol could significantly improve the blood flow in coronary collateral circulation after acute occlusion in this model.

  5. Acute phase protein response in an experimental model of ovine caseous lymphadenitis

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    Lang Tamara L

    2007-12-01

    Full Text Available Abstract Background Caseous lymphadenitis (CLA is a disease of small ruminants caused by Corynebacterium pseudotuberculosis. The pathogenesis of CLA is a slow process, and produces a chronic rather than an acute disease state. Acute phase proteins (APP such as haptoglobin (Hp serum amyloid A (SAA and α1 acid glycoprotein (AGP are produced by the liver and released into the circulation in response to pro-inflammatory cytokines. The concentration of Hp in serum increases in experimental CLA but it is not known if SAA and AGP respond in parallel or have differing response profiles. Results The concentration in serum of Hp, SAA and AGP in 6 sheep challenged with 2 × 105 cells of C. pseudotuberculosis showed significant increases (P C. pseudotuberculosis became detectable at 11 days p.i. and continued to rise throughout the experiment. Conclusion The serum concentrations of Hp, SAA and AGP were raised in sheep in an experimental model of CLA. An extended response was found for AGP which occurred at a point when the infection was likely to have been transforming from an acute to a chronic phase. The results suggest that AGP could have a role as a marker for chronic conditions in sheep.

  6. Blood gas stability and hematological changes in experimentally-induced acute porcine pleuropneumonia.

    Science.gov (United States)

    Kiorpes, A L; Mirsky, M L; MacWilliams, P S; Bäckström, L R; Collins, M T

    1989-01-01

    Blood gas and hematological responses to acute, mild Actinobacillus pleuropneumoniae infection of growing pigs was studied. Six pigs (average weight 10.1 kg) were experimentally infected intranasally with A. pleuropneumoniae serotype 5. Four pigs served as controls. Rectal temperatures and arterial blood for gas analysis and hematology were taken at 0, 8, 16, 24, 48 and 72 h postinfection. All infected pigs became febrile showing clinical signs typical of mild to moderate porcine pleuropneumonia; controls remained asymptomatic. Neutrophilia with bands and lymphopenia were observed only in infected pigs. Arterial partial pressures of O2 and CO2, and pH did not change in infected pigs. All pigs were killed after 72 h, and lungs were examined and cultured. Gross and microscopic lesions consistent with porcine pleuropneumonia were seen in 3/6 and 5/6 infected lungs, respectively. Control lungs were grossly normal with no histological evidence of pleuropneumonia. We conclude that in mild, acute porcine pleuropneumonia as established experimentally, a leukogram typical of acute inflammation and stress is seen; however, hypoxemia and alveolar hypoventilation are not features of this form of the disease. PMID:2914231

  7. Involvement of exosomes in lung inflammation associated with experimental acute pancreatitis.

    Science.gov (United States)

    Bonjoch, Laia; Casas, Vanessa; Carrascal, Montserrat; Closa, Daniel

    2016-10-01

    A frequent complication of acute pancreatitis is the lung damage associated with the systemic inflammatory response. Although various pro-inflammatory mediators generated at both local and systemic levels have been identified, the pathogenic mechanisms of the disease are still poorly understood. In recent years, exosomes have emerged as a new intercellular communication system able to transfer encapsulated proteins and small RNAs and protect them from degradation. Using an experimental model of taurocholate-induced acute pancreatitis in rats, we aimed to evaluate the role of exosomes in the extent of the systemic inflammatory response. Induction of pancreatitis increased the concentration of circulating exosomes, which showed a different proteomic profile to those obtained from control animals. A series of tracking experiments using PKH26-stained exosomes revealed that circulating exosomes effectively reached the alveolar compartment and were internalized by macrophages. In vitro experiments revealed that exosomes obtained under inflammatory conditions activate and polarize these alveolar macrophages towards a pro-inflammatory phenotype. Interestingly, the proteomic analysis of circulating exosomes during acute pancreatitis suggested a multi-organ origin with a relevant role for the liver as a source of these vesicles. Tracking experiments also revealed that the liver retains the majority of exosomes from the peritoneal cavity. We conclude that exosomes are involved in the lung damage associated with experimental acute pancreatitis and could be relevant mediators in the systemic effects of pancreatitis. Copyright © 2016 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd. Copyright © 2016 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.

  8. Acute phase response in two consecutive experimentally induced E. coli intramammary infections in dairy cows

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    Saatsi Johanna

    2008-06-01

    Full Text Available Abstract Background Acute phase proteins haptoglobin (Hp, serum amyloid A (SAA and lipopolysaccharide binding protein (LBP have suggested to be suitable inflammatory markers for bovine mastitis. The aim of the study was to investigate acute phase markers along with clinical parameters in two consecutive intramammary challenges with Escherichia coli and to evaluate the possible carry-over effect when same animals are used in an experimental model. Methods Mastitis was induced with a dose of 1500 cfu of E. coli in one quarter of six cows and inoculation repeated in another quarter after an interval of 14 days. Concentrations of acute phase proteins haptoglobin (Hp, serum amyloid A (SAA and lipopolysaccharide binding protein (LBP were determined in serum and milk. Results In both challenges all cows became infected and developed clinical mastitis within 12 hours of inoculation. Clinical disease and acute phase response was generally milder in the second challenge. Concentrations of SAA in milk started to increase 12 hours after inoculation and peaked at 60 hours after the first challenge and at 44 hours after the second challenge. Concentrations of SAA in serum increased more slowly and peaked at the same times as in milk; concentrations in serum were about one third of those in milk. Hp started to increase in milk similarly and peaked at 36–44 hours. In serum, the concentration of Hp peaked at 60–68 hours and was twice as high as in milk. LBP concentrations in milk and serum started to increase after 12 hours and peaked at 36 hours, being higher in milk. The concentrations of acute phase proteins in serum and milk in the E. coli infection model were much higher than those recorded in experiments using Gram-positive pathogens, indicating the severe inflammation induced by E. coli. Conclusion Acute phase proteins would be useful parameters as mastitis indicators and to assess the severity of mastitis. If repeated experimental intramammary

  9. Plasmid DNA immunization with Trypanosoma cruzi genes induces cardiac and clinical protection against Chagas disease in the canine model

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    Rodríguez-Morales Olivia

    2012-11-01

    Full Text Available Abstract The only existing preventive measure against American trypanosomosis, or Chagas disease, is the control of the transmitting insect, which has only been effective in a few South American regions. Currently, there is no vaccine available to prevent this disease. Here, we present the clinical and cardiac levels of protection induced by expression to Trypanosoma cruzi genes encoding the TcSP and TcSSP4 proteins in the canine model. Physical examination, diagnostic chagasic serology, and serial electrocardiograms were performed before and after immunization, as well as after experimental infection. We found that immunization with recombinant plasmids prevented hyperthermia in the acute phase of experimental infection and produced lymphadenomegaly as an immunological response against the parasite and additionally prevented heart rate elevation (tachycardia in the acute and/or chronic stages of infection. Immunization with T. cruzi genes encoding the TcSP and TcSSP4 antigens diminished the quality and quantity of the electrocardiographic abnormalities, thereby avoiding progression to more severe developments such as right bundle branch block or ventricular premature complexes in a greater number of dogs.

  10. Epidemiology of Chagas disease in Ecuador. A brief review

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    H Marcelo Aguilar V

    1999-09-01

    Full Text Available Chagas disease is a complex public health problem that has been underestimated in Ecuador. Here we review the relevant published information, and present unpublished and new data that help to understand the current Chagas disease epidemiological situation and its evolution in the country. Three main characteristics have been identified: (i persistence of Trypanosoma cruzi transmission in already known foci; (ii a marked endemicity in some urban areas of Guayaquil; and (iii the transformation of new Amazon foci into truly endemic areas. The situation in other suspect areas remains uncertain. Five Triatominae species have been implicated in the transmission of T. cruzi to people in Ecuador (Triatoma dimidiata, Rhodnius ecuadoriensis, R. pictipes, R. robustus and Panstrongylus geniculatus, but some others may also play a role in some areas (P. rufotuberculatus, P. howardi, T. carrioni and P. chinai. Other Triatominae reported seem to have little or no epidemiological relevance (T. venosa, T. dispar, Eratyrus mucronatus, E. cuspidatus, P. lignarius and Cavernicola pilosa. High frequency of acute cases and severe chronic disease has been observed. Although cardiomyopathy is more frequent, serious digestive disease is also present. It is estimated that around 120,000-200,000 people may be infected. 2.2 to 3.8 million people are estimated to live under transmission risk conditions.

  11. Evaluation of the rabbit as a model for Chagas disease - II: histopathologic studies of the heart, digestive tract and skeletal muscle

    Directory of Open Access Journals (Sweden)

    Arnaldo Moreira da Silva

    1996-04-01

    Full Text Available In order to investigate the value of the rabbit as an experimental model for Chagas' disease, seventy one animals were inoculated with different Trypanosoma cruzi strains and routes. The rabbits were submitted to necropsy in acute (earlier than three months of infection, recent chronic (three to six months and late chronic (later than six months phases. Myocarditis, generally focal and endomysial, occurred in 94.1%, 66.7% and 70.8% of the infected rabbits respectively in the acute, recent chronic and late chronic phases. The myocardial inflammatory exudate was composed by mononuclear cells, and also polymorphonuclear cells in the acute phase. In most cases of the late chronic phase, the myocarditis was similar to that described in the indeterminate form of human chagasic patients. Initial fibrosis occurred in the three phases but was more severe and frequent in the early chronic. Advanced fibrosis occurred only in the late chronic phase. Tissue parasites occurred only in the acute phase. The digestive tract and skeletal muscles showed mild and occasional lesions. Our data indicate that experimentally infected chagasic rabbits repeat some lesions similar to that of humans chagasic patients, specially that of the indeterminate form. So, it may be a useful, however not an ideal, model.

  12. Acute phase proteins in bovine milk in an experimental model of Staphylococcus aureus subclinical mastitis

    DEFF Research Database (Denmark)

    Eckersall, P D; Young, F J; Nolan, A M

    2006-01-01

    The objectives were to establish the origin of 2 acute phase proteins in milk during subclinical bovine mastitis and to characterize the relationship between those proteins in milk and blood. Haptoglobin (Hp) and mammary-associated serum amyloid A (M-SAA3) appear in milk during mastitis, whereas Hp...... and serum amyloid A increase in serum during mastitis. The concentrations of these proteins were determined in an experimental model using a field strain of Staphylococcus aureus to induce subclinical mastitis in dairy cows. The expression of mRNA coding for these proteins was assessed and the presence of M...

  13. Ischemic stroke classification and risk of embolism in patients with Chagas disease.

    Science.gov (United States)

    Montanaro, Vinícius Viana Abreu; da Silva, Creuza Maria; de Viana Santos, Carla Verônica; Lima, Maria Inacia Ruas; Negrão, Edson Marcio; de Freitas, Gabriel R

    2016-12-01

    Ischemic stroke (IS) and Chagas disease are strongly related. Nevertheless, little attention has been paid to this association and its natural history. The current guidelines concerning the management and secondary prevention of IS are largely based on the incomplete information or extrapolation of knowledge from other stroke etiologies. We performed a retrospective study which compared stroke etiologies among a cohort of hospitalized patients with IS and Chagas disease. The Instituto de Pesquisa Evandro Chagas/Fundação Oswaldo Cruz (IPEC/FIOCRUZ) embolic score was also used to identify and evaluate the risk of embolism in this population. A total of 86 patients were included in the analysis. The mean age of the study population was 58 years, and 60 % were men. According to the Trial of Org 10172 in Acute Stroke Treatment (TOAST) Classification, 45 % of the strokes were of undetermined etiology and 45 % of cardioembolic origin, while the Stop Stroke Study/Causative Classification System (SSS/CCS) TOAST indicated that 34 % were undetermined and 50 % cardioembolic (p Chagas disease. The IPEC/FIOCRUZ score did not correlate with the number of patients who were determined to have cardioembolic stroke etiologies. The current guidelines for stroke prevention should be reviewed in this population.

  14. Enfermedad de Chagas en Colombia

    Directory of Open Access Journals (Sweden)

    Fernando Serpa Florez

    1985-12-01

    Full Text Available

    Generalidades.

    La tripanosomiasis americana o enfermedad de Chagas se halla ampliamente distribuida en Centro y Sur América. La Organización Mundial de la Salud considera que pueden haber doce millones de casos de esta dolencia en el continente (1, estudiados principalmente en Argentina, Brasil y Venezuela. Se calcula que en Colombia tendríamos una incidencia muy alta de casos, (Marinkelle (2 estima que 7.140/0 de la población podría estar infectada o sea cerca de dos millones de personas, distribuidos en las zonas rurales del nordeste del país (cuenca del Catatumbo Magdalena Medio y Llanos Orientales (Piedemonte, Macarena y Meta cercano (3 (4 (5 Y que seis millones de nuestros compatriotas -22.30/0 de la población total- (2 corren el riesgo de adquirir la enfermedad pues habitan en regiones donde se dan las condiciones para que ésta se propague.


    RESEÑA HISTORICA DE LA ENFERMEDAD EN COLOMBIA
    La existencia de casos de tripanosomiasis americana y de sus vectores fue comprobada en Colombia desde 1929 cuando César Uribe Piedrahita (6 encontró en Prado, Tolima, vectores del mal infectados con T.

    cruzi e Ignacio Moreno Pérez observó dicho hemoflagelado en sangre de seres humanos en Cali (4. En los años siguientes Hernando Ucrós, Benjamín Otálora, Hernando Groot, Santiago Renjifo, Hernando Osorno, Carlos Duarte Rangel, C.J. Marinkelle, Augusto Corredor, Ernesto Suescún y varios otros investigadores colomb iano s describieron diversos focos de la enfermedad en Colombia y estudiaron la distribución de sus vectores y huéspedes intermediarios. En 1947 1. Caicedo y C. Hernández publicaron su informe sobre los primeros casos crónicos de enfermedad de Chagas comprobados en nuestro país, procedentes de la región de Fusagasugá, Cundinamarca (7 en tanto que, en 1961, Marcos Duque inicia los estudios sobre cardiopatía chagásica (8 y Hernando Rocha, en 1971, comunica

  15. Experimentally derived acute and chronic copper Biotic Ligand Models for rainbow trout.

    Science.gov (United States)

    Crémazy, Anne; Wood, Chris M; Ng, Tania Y-T; Smith, D Scott; Chowdhury, M Jasim

    2017-11-01

    with the pH. Additional mechanistic studies are required to understand the influence of pH, Na, and Mg on Cu toxicity to trout. The present study presents the first experimentally developed chronic Cu BLM for the rainbow trout. To the best of our knowledge, it also presents the first acute Cu BLM that is based on a published data-set for trout. These newly developed BLMs should contribute to improving the risk assessment of Cu to fish in freshwater. Copyright © 2017. Published by Elsevier B.V.

  16. Tissue Pharmacology of Da-Cheng-Qi Decoction in Experimental Acute Pancreatitis in Rats

    Directory of Open Access Journals (Sweden)

    Xianlin Zhao

    2015-01-01

    Full Text Available Objectives. The Chinese herbal medicine Da-Cheng-Qi Decoction (DCQD can ameliorate the severity of acute pancreatitis (AP. However, the potential pharmacological mechanism remains unclear. This study explored the potential effective components and the pharmacokinetic characteristics of DCQD in target tissue in experimental acute pancreatitis in rats. Methods. Acute pancreatitis-like symptoms were first induced in rats and then they were given different doses of DCQD (6 g/kg, 12 g/kg, and 24 g/kg body weight orally. Tissue drug concentration, tissue pathological score, and inflammatory mediators in pancreas, intestine, and lung tissues of rats were examined after 24 hours, respectively. Results. Major components of DCQD could be found in target tissues and their concentrations increased in conjunction with the intake dose of DCQD. The high-dose compounds showed maximal effect on altering levels of anti-inflammatory (interleukin-4 and interleukin-10 and proinflammatory markers (tumor necrosis factor α and interleukin-6 and ameliorating the pathological damage in target tissues P<0.05. Conclusions. DCQD could alleviate pancreatic, intestinal, and lung injury by altering levels of inflammatory cytokines in AP rats with tissue distribution of its components.

  17. Effects of Schizolobium parahyba extract on experimental Bothrops venom-induced acute kidney injury.

    Directory of Open Access Journals (Sweden)

    Monique Silva Martines

    Full Text Available BACKGROUND: Venom-induced acute kidney injury (AKI is a frequent complication of Bothrops snakebite with relevant morbidity and mortality. The aim of this study was to assess the effects of Schizolobium parahyba (SP extract, a natural medicine with presumed anti-Bothrops venom effects, in an experimental model of Bothrops jararaca venom (BV-induced AKI. METHODOLOGY: Groups of 8 to 10 rats received infusions of 0.9% saline (control, C, SP 2 mg/kg, BV 0.25 mg/kg and BV immediately followed by SP (treatment, T in the doses already described. After the respective infusions, animals were assessed for their glomerular filtration rate (GFR, inulin clearance, renal blood flow (RBF, Doppler, blood pressure (BP, intra-arterial transducer, renal vascular resistance (RVR, urinary osmolality (UO, freezing point, urinary neutrophil gelatinase-associated lipocalin (NGAL, enzyme-linked immunosorbent assay [ELISA], lactate dehydrogenase (LDH, kinetic method, hematocrit (Hct, microhematocrit, fibrinogen (Fi, Klauss modified and blinded renal histology (acute tubular necrosis score. PRINCIPAL FINDINGS: BV caused significant decreases in GFR, RBF, UO, HcT and Fi; significant increases in RVR, NGAL and LDH; and acute tubular necrosis. SP did not prevent these changes; instead, it caused a significant decrease in GFR when used alone. CONCLUSION: SP administered simultaneously with BV, in an approximate 10∶1 concentration, did not prevent BV-induced AKI, hemolysis and fibrinogen consumption. SP used alone caused a decrease in GFR.

  18. Novel drug discovery for Chagas disease.

    Science.gov (United States)

    Moraes, Carolina B; Franco, Caio H

    2016-01-01

    Chagas disease is a chronic infection associated with long-term morbidity. Increased funding and advocacy for drug discovery for neglected diseases have prompted the introduction of several important technological advances, and Chagas disease is among the neglected conditions that has mostly benefited from technological developments. A number of screening campaigns, and the development of new and improved in vitro and in vivo assays, has led to advances in the field of drug discovery. This review highlights the major advances in Chagas disease drug screening, and how these are being used not only to discover novel chemical entities and drug candidates, but also increase our knowledge about the disease and the parasite. Different methodologies used for compound screening and prioritization are discussed, as well as novel techniques for the investigation of these targets. The molecular mechanism of action is also discussed. Technological advances have been executed with scientific rigour for the development of new in vitro cell-based assays and in vivo animal models, to bring about novel and better drugs for Chagas disease, as well as to increase our understanding of what are the necessary properties for a compound to be successful in the clinic. The gained knowledge, combined with new exciting approaches toward target deconvolution, will help identifying new targets for Chagas disease chemotherapy in the future.

  19. The main sceneries of Chagas disease transmission. The vectors, blood and oral transmissions - A comprehensive review

    Directory of Open Access Journals (Sweden)

    José Rodrigues Coura

    2015-05-01

    Full Text Available This review deals with transmission of Trypanosoma cruzi by the most important domestic vectors, blood transfusion and oral intake. Among the vectors, Triatoma infestans, Panstrongylus megistus, Rhodnius prolixus, Triatoma dimidiata, Triatoma brasiliensis, Triatoma pseudomaculata, Triatoma sordida, Triatoma maculata, Panstrongylus geniculatus, Rhodnius ecuadoriensis and Rhodnius pallescens can be highlighted. Transmission of Chagas infection, which has been brought under control in some countries in South and Central America, remains a great challenge, particularly considering that many endemic countries do not have control over blood donors. Even more concerning is the case of non-endemic countries that receive thousands of migrants from endemic areas that carry Chagas disease, such as the United States of America, in North America, Spain, in Europe, Japan, in Asia, and Australia, in Oceania. In the Brazilian Amazon Region, since Shaw et al. (1969 described the first acute cases of the disease caused by oral transmission, hundreds of acute cases of the disease due to oral transmission have been described in that region, which is today considered to be endemic for oral transmission. Several other outbreaks of acute Chagas disease by oral transmission have been described in different states of Brazil and in other South American countries.

  20. Mitochondrial dysfunction in peripheral blood mononuclear cells in early experimental and clinical acute pancreatitis.

    Science.gov (United States)

    Chakraborty, Mandira; Hickey, Anthony J R; Petrov, Maxim S; Macdonald, Julia R; Thompson, Nichola; Newby, Lynette; Sim, Dalice; Windsor, John A; Phillips, Anthony R J

    2016-01-01

    Mitochondrial dysfunction occurs in vital organs in experimental acute pancreatitis (AP) and may play an important role in determining severity of AP. However, obtaining vital organ biopsies to measure mitochondrial function (MtF) in patients with AP poses considerable risk of harm. Being able to measure MtF from peripheral blood will bypass this problem. Furthermore, whether mitochondrial dysfunction is detectable in peripheral blood in mild AP is unknown. Therefore, the objective was to evaluate peripheral blood MtF in experimental and clinical AP. Mitochondrial respiration was measured using high resolution oxygraphy in an experimental study in caerulein induced AP and in a separate study, in patients with mild AP. Superoxide, cytochrome c, mitochondrial membrane potential (ΔΨ) and adenine triphosphate (ATP) were also measured as other markers of MtF. Even though some states of mitochondrial respiration were increased in both experimental and clinical AP, this did not lead to an increase in net ATP in patients with AP. The increased leak respiration in both studies was further proof of dyscoupled mitochondria. In the clinical study there were also features of mitochondrial dysfunction with increased leak flux control ratio, superoxide, ΔΨ and decreased cytochrome c. There is evidence of mitochondrial dysfunction with dyscoupled mitochondria, increased superoxide and decreased cytochrome c in patients with mild acute pancreatitis. Further studies should now determine whether mitochondrial function alters with severity in AP and whether mitochondrial dysfunction responds to treatments. Copyright © 2016 IAP and EPC. Published by Elsevier B.V. All rights reserved.

  1. Organ microcirculatory disturbances in experimental acute pancreatitis. A role of nitric oxide.

    Science.gov (United States)

    Dobosz, M; Hac, S; Mionskowska, L; Dymecki, D; Dobrowolski, S; Wajda, Z

    2005-01-01

    Microcirculatory disturbances are important early pathophysiological events in various organs during acute pancreatitis (AP). The aim of the study was to investigate an influence of L-arginine (nitric oxide substrate) and N(G)-nitro-L-arginine (L-NNA, nitric oxide synthase inhibitor) on organ microcirculation in experimental acute pancreatitis induced by four consecutive intraperitoneal cerulein injections (15 microg/kg/h). The microcirculation of pancreas, liver, kidney, stomach, colon and skeletal muscle was measured by laser Doppler flowmeter. Serum interleukin 6 and hematocrit levels were analyzed. AP resulted in a significant drop of microperfusion in all examined organ. L-arginine administration (2 x 100 mg/kg) improved the microcirculation in the pancreas, liver, kidney, colon and skeletal muscle, and lowered hematocrit levels. L-NNA treatment (2 x 25 mg/kg) caused aggravation of edematous AP to the necrotizing situation, and increased IL-6 and hematocrit levels. A further reduction of blood perfusion was noted in the stomach only. It is concluded that L-arginine administration has a positive influence on organ microcirculatory disturbances accompanying experimental cerulein-induced AP. NO inhibition aggravates the course of pancreatitis.

  2. Blockade of Rennin-Angiotensin system blunts the fibrotic response in experimental acute pyelonephritis

    Directory of Open Access Journals (Sweden)

    Singal A

    2005-01-01

    Full Text Available Aim: To study the impact of Renin-Angiotensin system blockade in experimental acute pyelonephritis, induced by a novel surgical approach via dorsal lumbotomy incision. Materials and Methods : 45 Adult female WISTAR rats aged 8-12 weeks, underwent direct inoculation of 0.1 ml of E.coli suspension into the parenchyma of the surgically exposed kidney. 3 groups of rats were studied: Group A - treated with antibiotics only; Group B- Captopril and antibiotics and Group C- Losartan and antibiotics. Changes of acute inflammation, parenchymal destruction and scarring were compared between the groups on histopathological sections. Kruskal-Wallis test was used for statistical analysis. Results : Changes consistent with acute pyelonephritis were seen in all the kidneys. Mean% scar area in Group A, Group B and Group C was 37.08±1.79, 24.40±1.88 and 24.68±1.32% respectively at end of six weeks. Mean tubular density in Group A, B and C was 17.26±1.92, 47.18±3.00 and 47.00±5.08-tubules/lac mm2 respectively. The differences between the control and the treated animals were significant, though the results did not differ between the losartan and captopril treated rats. Conclusions : Dorsal lumbotomy approach to the kidney provides a good exposure of the kidney. Induction of acute pyelonephritis by direct inoculation of bacteria into renal cortex produced a consistent scar at 6 weeks. Blockade of renin angiotensin system by either captopril or losartan decreased the renal scar area by almost 1/3 at 6 weeks.

  3. Evaluation of the efficacy of curcumin in experimentally induced acute sinusitis in rats.

    Science.gov (United States)

    Birdane, Leman; Cingi, Cemal; Muluk, Nuray Bayar; San, Turhan; Burukoglu, Dilek

    2016-12-01

    We investigated the possible beneficial effects of curcumin (CMN) in the treatment of sinusitis. An experimentally induced sinusitis model was created in rats, and the results were evaluated histologically. Thirty-two healthy, female Sprague Dawley rats weighing 270 to 310 g each, were randomly divided into four groups. Group 1 was the control group. In Groups 2 to 4, experimentally induced acute sinusitis was developed, and the rats in those groups were given saline, sulbactam-ampicillin, and CMN, respectively, for 10 days. Then all rats were dissected, and samples of sinus mucosa were taken. Histologic examination was performed via light microscopy. In the sinusitis + antibiotic group, values of inflammation, vascular congestion, vascular dilatation, and subepithelial glandular atrophy were significantly higher; and values of mucosal damage and cilia loss, and hyperplasia of goblet cells, were not significantly different from those in the control group. In the sinusitis + CMN group, values of inflammation, vascular congestion, and vascular dilatation were significantly higher; and values of mucosal damage and cilia loss, hyperplasia of goblet cells, and subepithelial glandular atrophy were not significantly different from those of the control group. Histologic examination revealed that in the sinusitis + CMN group, a nearly normal appearance of the epithelial tissue and reduced cellular inflammation in connective tissue were observed. Minimal vascular congestion in connective tissue remained. The efficacy of CMN in acute sinusitis may be related to its potent anti-inflammatory effects on modulation of various inflammatory cytokines. When low side effects are taken into account, CMN therapy may be a promising option in the treatment of acute sinusitis.

  4. Lymphatic Leukaemia* In Acute

    African Journals Online (AJOL)

    A case report of a patient who developed fatal pneumo- cystis pneumonia while in remission from acute lymphatic ... Chagas and CariniY This rare and usually fatal disease occurs in young babies;" or in individuals whose ... was then a month since his illness had started. On admission to our clinic we found the following: ...

  5. Lack of association between serum syndecan-4, myocardial fibrosis and ventricular dysfunction in subjects with chronic Chagas disease.

    Science.gov (United States)

    Larocca, Ticiana Ferreira; Macêdo, Carolina Thé; Noya-Rabelo, Márcia; Lemos Correia, Luís Cláudio; Moreira, Moisés Imbassahy; Caldas, Alessandra Carvalho; Torreão, Jorge Andion; Souza, Bruno Solano de Freitas; Vasconcelos, Juliana Fraga; Carvalho da Silva, Alexandre Schaer; Ribeiro Dos Santos, Ricardo; Soares, Milena Botelho Pereira

    2017-01-01

    Syndecan-4 is a transmembrane glycoprotein associated with inflammation and fibrosis. Increased syndecan-4 levels were previously detected after acute myocardial infarction and in subjects with heart failure. However, the levels of syndecan-4 in subjects with Chagas disease have not so far been investigated. The aim of this study was to investigate the potential role of serum sydencan-4 as a novel biomarker for myocardial fibrosis and cardiac dysfunction in subjects with Chagas disease. This study comprised subjects with Chagas disease (n = 56), being 14 (25%) with the indeterminate form, 16 (29%) with the cardiac form without ventricular dysfunction, and 26 (46%) with the cardiac form with ventricular dysfunction. Syndecan-4 serum concentrations did not correlate with presence or absence of myocardial fibrosis (P = 0.386) nor disease severity in subjects with Chagas disease (P = 0.918). Additionally, no correlation was found either between the degree of myocardial fibrosis and serum syndecan-4 [r = 0.08; P = 0.567] or between left ventricular ejection fraction and syndecan-4 [r = 0.02; P = 0.864]. In contrast, NT-proBNP levels correlated with ejection fraction and myocardial fibrosis. Our results demonstrate the lack of correlations between serum syndecan-4, myocardial fibrosis and cardiac dysfunction in subjects with Chagas disease. Further studies are required to show if syndecan-4 concentrations can be marker for prognosis assessment or disease progression.

  6. Does a spontaneous cure for chagas' disease exist?

    Directory of Open Access Journals (Sweden)

    Rodrigo Zeledón

    1988-03-01

    Full Text Available Six Costa Rican Chagas' disease patients, with wellknown acute phase history and no specific treatment were examined in several occasions during 39, 24, 32, 16 and 14 years, respectively, from the onset. Nome of the patients presented heart abnormalities as revealed by the conventional EKG and ergometry, exceptfor one of them with an incomplete block of the right bundle branch. Also, no alterations of the oesophagus motility was detected manometrically except for another patient who presented a slight hypersensivity reaction to a pharmacological test (Mecholyl. Three out of six patients became serologically negative in 1981, remaining as such until 1986. Besides the conventional serology, the search of protective ("lytic" antibodies was also performed in 1985 and 1986, being completely negative in one of the "cured" patients and dubious in the other two. The hypothesis that these three patients had as spontaneous cure, based on the clinical, serological and parasitologica l findings is discussed.

  7. Lung Functional and Biologic Responses to Variable Ventilation in Experimental Pulmonary and Extrapulmonary Acute Respiratory Distress Syndrome.

    Science.gov (United States)

    Samary, Cynthia S; Moraes, Lillian; Santos, Cintia L; Huhle, Robert; Santos, Raquel S; Ornellas, Debora S; Felix, Nathane S; Capelozzi, Vera L; Schanaider, Alberto; Pelosi, Paolo; de Abreu, Marcelo Gama; Rocco, Patricia R M; Silva, Pedro L

    2016-07-01

    The biologic effects of variable ventilation may depend on the etiology of acute respiratory distress syndrome. We compared variable and conventional ventilation in experimental pulmonary and extrapulmonary acute respiratory distress syndrome. Prospective, randomized, controlled experimental study. University research laboratory. Twenty-four Wistar rats. Acute respiratory distress syndrome was induced by Escherichia coli lipopolysaccharide administered intratracheally (pulmonary acute respiratory distress syndrome, n = 12) or intraperitoneally (extrapulmonary acute respiratory distress syndrome, n = 12). After 24 hours, animals were randomly assigned to receive conventional (volume-controlled ventilation, n = 6) or variable ventilation (n = 6). Nonventilated animals (n = 4 per etiology) were used for comparison of diffuse alveolar damage, E-cadherin, and molecular biology variables. Variable ventilation was applied on a breath-to-breath basis as a sequence of randomly generated tidal volume values (n = 600; mean tidal volume = 6 mL/kg), with a 30% coefficient of variation (normal distribution). After randomization, animals were ventilated for 1 hour and lungs were removed for histology and molecular biology analysis. Variable ventilation improved oxygenation and reduced lung elastance compared with volume-controlled ventilation in both acute respiratory distress syndrome etiologies. In pulmonary acute respiratory distress syndrome, but not in extrapulmonary acute respiratory distress syndrome, variable ventilation 1) decreased total diffuse alveolar damage (median [interquartile range]: volume-controlled ventilation, 12 [11-17] vs variable ventilation, 9 [8-10]; p ventilation, 21.5 [18.3-23.3] vs variable ventilation, 5.6 [4.6-12.1]; p ventilation, 2.0 [1.3-2.1] vs variable ventilation, 0.7 [0.6-1.4]; p ventilation, 0.3 [0.2-0.5] vs variable ventilation, 0.8 [0.5-1.3]; p ventilation increased vascular cell adhesion molecule-1 messenger RNA expression (volume

  8. [Therapeutic experience in a Chagas disease center].

    Science.gov (United States)

    Abramson, Raúl; Figueroa, Patricia

    2013-11-01

    American Trypanosomiasis or Chagas Disease is a major public health problem, endemic in the American continent since prehistoric times. Its natural course is towards chronicity in the immunocompetent host, often leading to severe cardiopathy or bowel involvement. Pharmacologic therapy is restricted to two drugs and only one of them is currently available in Chile. Both have poor effectiveness in the chronic stages of the disease and cause frequent adverse reactions. Many physicians avoid their use, despite published evidences about the usefulness. We herein report the experience of our Center in the treatment of Chronic Chagas Disease in adults using the drug nifurtimox, emphasizing its degree of acceptability and its secondary effects.

  9. Immunosuppression and Chagas disease; experience from a non-endemic country.

    Science.gov (United States)

    Salvador, F; Sánchez-Montalvá, A; Valerio, L; Serre, N; Roure, S; Treviño, B; Pou, D; Sulleiro, E; Bocanegra, C; Molina, I

    2015-09-01

    Reactivation of Chagas disease in the chronic phase may occur when immunosuppression is established, sometimes resulting in high parasitaemia and severe clinical manifestations such as meningitis and meningoencephalitis. Although this situation is being increasingly described, there is still scarce information. This retrospective observational study was performed in three Tropical Medicine Units of Barcelona (Spain) included in the International Health Programme of the Catalan Health Institute (PROSICS). The objective of the study was to describe epidemiological, clinical, microbiological, prognostic and therapeutic data from patients with Chagas disease and any kind of immunosuppressive condition attended in these three institutions from January 2007 to October 2014. From 1823 patients with Chagas disease attending these three centres during the study period, 38 (2%) had some kind of immunosuppressive condition: 12 patients had human immunodeficiency virus infection, 8 patients had neoplasia, 4 patients underwent organ transplantation and 14 patients had an autoimmune disease. Eight (21.1%) patients had cardiac involvement, and six (15.8%) patients had gastrointestinal involvement. Acute Trypanosoma cruzi infection was detected in two Spanish patients. Thirty-one (81.6%) patients received treatment with benznidazole, of whom 17 (54.8%) had some kind of adverse event. No patient had a severe manifestation or reactivation of Chagas disease. Patients with Chagas disease under immunosuppressive conditions are being increasingly described, especially in non-endemic countries. More information about this topic is required and international consensus in the diagnosis, treatment and follow up of these patients must be established to reduce the morbidity and mortality. Copyright © 2015 European Society of Clinical Microbiology and Infectious Diseases. Published by Elsevier Ltd. All rights reserved.

  10. Technological innovation strategies for the specific treatment of Chagas disease based on Benznidazole.

    Science.gov (United States)

    de Moura Ferraz, Leslie Raphael; Alves, Alinne Élida Gonçalves; da Silva Nascimento, Débora Dolores Souza; E Amariz, Isabela Araújo; Ferreira, Aline Silva; Costa, Salvana Priscylla Manso; Rolim, Larissa Araújo; de Lima, Ádley Antonini Neves; Neto, Pedro José Rolim

    2018-02-13

    Caused by Trypanosoma cruzi, Chagas disease is responsible for public health problems greater in magnitude than those attributed to malaria, schistosomiasis, or leishmaniasis. A factor in the socioeconomic development of poor countries, Chagas disease can cause death due to a high parasitic burden during its acute phase due and irreversible damage in organs such as the heart, esophagus, and colon during its chronic phase, even when the number of parasites is minimal. For treating Chagas disease, benznidazole (BNZ) remains the drug of choice and, in Latin America, the only drug on the market for treating the disease. However, BNZ has exhibited insufficient activity in the chronic phase of Chagas disease, required administration in large doses, prolonged treatment, and shown a high incidence of adverse reactions (vomiting, rash, peripheral neuropathy, and spinal cord depression), toxicity, and low solubility in water. As an antidote, pharmaceutical technologies have been introduced that can improve BNZ's solubility and dissolution, as well as reduce side effects in light of its bioavailability, all of which can enhance therapy for Chagas disease. In response to that trend, by conducting a literature review, we sought to identify current pharmaceutical technologies used in tandem with BNZ to improve therapy for Chagas disease. Documented techniques include emulsion and microemulsion formation, solutions, parenteral formulas, micronization, and drug delivery systems supported by the development of nanoparticles and cyclodextrins, solid dispersions, and the use of metal-organic frameworks as innovative excipients. Such technologies increase the water solubility of BNZ by 4-25-fold on dissolution and an 85% release with efficacy in only a few minutes, as recorded during a viability experiment with nanoparticle suspensions. That experiment demonstrated the need for a lower concentration of BNZ to kill 50% of trypomastigote forms of T. cruzi, described in terms of the

  11. Greater resistance of the rabbit antropyloric region to experimental acute gastric ischemia

    Directory of Open Access Journals (Sweden)

    Maria Angélica B. Magalhães

    2013-08-01

    Full Text Available INTRODUCTION: Gastric ischemia represents an important medical challenge in pathology and surgical practice. OBJECTIVE: The purpose of this study was to assess the effects of acute gastric ischemia on different regions of the stomach. METHOD: Rabbit stomachs were subjected to devascularization of the greater and lesser curvatures for 3, 6 and 12 hours. After these periods, the stomachs were removed for macro and microscopic analysis. RESULTS: Hemorrhagic necrosis was more marked in the gastric fundus and body. In contrast, the antropylorus remained preserved in 100% of the rabbits after 3 hours of ischemia (group I, and in 80% of the rabbits after 6 and 12 hours of ischemia (groups II and III. Necrosis of the gastric body and fundus mucosa were observed in all animals after 6 and 12 hours of ischemia. CONCLUSION: We concluded that this experimental model of acute gastric ischemia was effective in producing hemorrhagic necrosis of the gastric fundus and body in rabbits even within a short period of time. Furthermore, the antropyloric region was preserved in most animals.

  12. Physiological and biochemical changes associated with acute experimental dehydration in the desert adapted mouse, Peromyscus eremicus.

    Science.gov (United States)

    Kordonowy, Lauren; Lombardo, Kaelina D; Green, Hannah L; Dawson, Molly D; Bolton, Evice A; LaCourse, Sarah; MacManes, Matthew D

    2017-03-01

    Characterizing traits critical for adaptation to a given environment is an important first step in understanding how phenotypes evolve. How animals adapt to the extreme heat and aridity commonplace to deserts is an exceptionally interesting example of these processes, and has been the focus of study for decades. In contrast to those studies, where experiments are conducted on either wild animals or captive animals held in non-desert conditions, the study described here leverages a unique environmental chamber that replicates desert conditions for captive Peromyscus eremicus (cactus mouse). Here, we establish baseline values for daily water intake and for serum electrolytes, as well as the response of these variables to acute experimental dehydration. In brief, P eremicus daily water intake is very low. Its serum electrolytes are distinct from many previously studied animals, and its response to acute dehydration is profound, though not suggestive of renal impairment, which is atypical of mammals. © 2017 The Authors. Physiological Reports published by Wiley Periodicals, Inc. on behalf of The Physiological Society and the American Physiological Society.

  13. Endotoxin tolerance alleviates experimental acute liver failure via inhibition of high mobility group box 1.

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    Yang, Nai-Bin; Ni, Shun-Lan; Li, Shan-Shan; Zhang, Sai-Nan; Hu, Dan-Ping; Lu, Ming-Qin

    2015-01-01

    High mobility group box 1 (HMGB1) has been widely reported to mediate damage caused by inflammatory responses. The aim of our study is to investigate the role of HMGB1 in endotoxin tolerance (ET) alleviating inflammation of acute liver failure (ALF) rats and its possible signaling mechanism. To mimic ET, male Sprague-Dawley rats were pretreated with low dose of lipopolysaccharide (LPS) (0.1 mg/kg once a day intraperitoneally for consecutive five days) before subsequent ALF induction. ALF was induced by intraperitoneal administration of D-GalN/LPS. ET induced by LPS pretreatment significantly improved the survival rate of ALF rats. Moreover, after ALF induction, ET+ALF rats exhibited lower serum enzyme (ALT, AST and TBiL) levels, lower production of inflammatory cytokines (IL-6, TNF-a and HMGB1) and more minor liver histopathological damage than ALF rats. ET+ALF rats showed enhanced expression levels of HMGB1, decreased levels of STAT1 and p-STAT1, augmented expression of SOCS1 in liver tissues than ALF rats. These results indicated that ET induced by low-dose LPS pretreatment may alleviate inflammation and liver injury in experimental acute liver failure rats mainly through inhibition of hepatic HMGB1 translocation and release.

  14. Montelukast is as effective as penicillin in treatment of acute otitis media: An experimental rat study

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    Uçar, Seçil; Huseynov, Tural; Çoban, Melahat; Sarıoğlu, Sülen; Şerbetçioğlu, Bülent; Yalcin, Arzu Didem

    2013-01-01

    Background Leukotrienes are the major factors in the formation of edema and mucus, as well as development of tuba Eustachii dysfunction in acute otitis media. We developed an experimental acute suppurative otitis media model and compared the responses of rats to penicillin and combinations of leukotriene antagonist with respect to histopathological observations conducted in early and late phases. Material/Methods A total of 83 ears from 56 Wistar rats were used in this study. Pneumococcus suspension was injected trans-tympanically into all rats. Subjects were classified into 4 different groups with 14 rats in each. In Group A, intramuscular penicillin G was injected for a period of 5 days. In Group B, intraperitoneal montelukast was injected for 21 days in addition to penicillin. In Group C, intraperitoneal montelukast isotonic NaCl in Group D was injected into rats for 21 days. Results No significant difference was found between the groups, except for mucosal vascularization with respect to mucosal and TM parameters in early phases. Furthermore, considerable deviations were observed for the recuperation of TM and mucosal inflammation for groups in which subjects were injected with montelukast as compared to other groups of the study in the late phases. Conclusions When the parameters of inflammation in the rat middle ear were compared with each other, most of these parameters did not show any statistically significant beneficial effects in montelukast and penicillin groups. PMID:24048018

  15. Association of Cardiac Galectin-3 Expression, Myocarditis, and Fibrosis in Chronic Chagas Disease Cardiomyopathy.

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    Souza, Bruno Solano de Freitas; Silva, Daniela Nascimento; Carvalho, Rejane Hughes; Sampaio, Gabriela Louise de Almeida; Paredes, Bruno Diaz; Aragão França, Luciana; Azevedo, Carine Machado; Vasconcelos, Juliana Fraga; Meira, Cassio Santana; Neto, Paulo Chenaud; Macambira, Simone Garcia; da Silva, Kátia Nunes; Allahdadi, Kyan James; Tavora, Fabio; de Souza Neto, João David; Dos Santos, Ricardo Ribeiro; Soares, Milena Botelho Pereira

    2017-05-01

    Chronic Chagas disease cardiomyopathy, caused by Trypanosoma cruzi infection, is a major cause of heart failure in Latin America. Galectin-3 (Gal-3) has been linked to cardiac remodeling and poor prognosis in heart failure of different etiologies. Herein, we investigated the involvement of Gal-3 in the disease pathogenesis and its role as a target for disease intervention. Gal-3 expression in mouse hearts was evaluated during T. cruzi infection by confocal microscopy and flow cytometry analysis, showing a high expression in macrophages, T cells, and fibroblasts. In vitro studies using Gal-3 knockdown in cardiac fibroblasts demonstrated that Gal-3 regulates cell survival, proliferation, and type I collagen synthesis. In vivo blockade of Gal-3 with N-acetyl-d-lactosamine in T. cruzi-infected mice led to a significant reduction of cardiac fibrosis and inflammation in the heart. Moreover, a modulation in the expression of proinflammatory genes in the heart was observed. Finally, histological analysis in human heart samples obtained from subjects with Chagas disease who underwent heart transplantation showed the expression of Gal-3 in areas of inflammation, similar to the mouse model. Our results indicate that Gal-3 plays a role in the pathogenesis of experimental chronic Chagas disease, favoring inflammation and fibrogenesis. Moreover, by demonstrating Gal-3 expression in human hearts, our finding reinforces that this protein could be a novel target for drug development for Chagas cardiomyopathy. Copyright © 2017 American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved.

  16. Acute pulmonary injury induced by experimental muscle trauma Lesão pulmonar aguda induzida por trauma muscular experimental

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    Márcia Andréa da Silva Carvalho Sombra

    2011-01-01

    Full Text Available PURPOSE: To develop an easily reproducible model of acute lung injury due to experimental muscle trauma in healthy rats. METHODS: Eighteen adult Wistar rats were randomized in 3 groups (n=6: G-1- control, G-2 - saline+trauma and G-3 - dexamethasone+trauma. Groups G-1 and G-2 were treated with saline 2,0ml i.p; G-3 rats were treated with dexamethasone (DE (2 mg/kg body weight i.p.. Saline and DE were applied 2h before trauma and 12h later. Trauma was induced in G-2 and G-3 anesthetized (tribromoethanol 97% 100 ml/kg i.p. rats by sharp section of anterior thigh muscles just above the knee, preserving major vessels and nerves. Tissue samples (lung were collected for myeloperoxidase (MPO assay and histopathological evaluation. RESULTS: Twenty-four hours after muscle injury there was a significant increase in lung neutrophil infiltration, myeloperoxidase activity and edema, all reversed by dexamethasone in G-3. CONCLUSION: Trauma by severance of thigh muscles in healthy rats is a simple and efficient model to induce distant lung lesions.OBJETIVO: Desenvolver um modelo facilmente reprodutível de lesão pulmonar aguda decorrente de trauma muscular experimental em ratos sadios. MÉTODOS: Dezoito ratos Wistar adultos foram randomizados em 3 grupos (n=6: G-1-controle, G-2 - trauma+salina e G-3 - trauma+dexametasona. Grupos G-1 e G-2 foram tratados com salina 2,0 ml ip, G-3 ratos foram tratados com dexametasona (DE (2 mg/kg peso corporal ip. Salina e DE foram aplicadas 2h antes e 12h depois do trauma. Trauma foi induzido em ratos G-2 e G-3 anestesiados (tribromoetanol 97% de 100 ml/kg, i.p. por secção da musculatura anterior da coxa logo acima da articulação do joelho, preservando os grandes vasos e nervos. Amostras de tecido (pulmão foram coletadas para avaliação da mieloperoxidase (MPO, e exames histopatológicos. RESULTADOS: Vinte e quatro horas após a indução da lesão muscular houve um aumento significativo na infiltração de neutr

  17. Neutrophil engagement and septic challenge in acute experimental pancreatitis in rats.

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    Hać, Stanisław; Dobosz, Marek; Kaczor, Jan-J; Rzepko, Robert; Aleksandrowicz-Wrona, Ewa; Wajda, Zdzisław; Sledziński, Zbigniew; Krajewski, Jacek

    2005-11-07

    To investigate the influence of neutrophil adhesion molecule blockade with monoclonal antibody (MoAb CD11b) and E. coli lipopolysaccharide (LPS) administration on experimental acute pancreatitis (AP). AP was induced by four ip injections of cerulein (Cn) at 1-h intervals. MoAb CD 11b and LPS were administered at the beginning of the experiment. The neutrophil count and chemiluminescence were diminished at the beginning of AP. The oxidative stress parameters were found within the pancreatic gland. MoAb CD 11b used for AP resulted in a significant reduction of pancreatic infiltration and pancreatitis oxidative stress parameters. Serum interleukin-6 (IL-6) was not detected in AP animals, whereas high serum IL-6 concentration was noted only in animals receiving LPS. Neutrophils are involved in pancreatic damage in the early stage of AP. Neutrophil infiltration reduction protects the pancreatic gland from destruction during AP. LPS does not change the early course of Cn pancreatitis in rats.

  18. Housing Interventions and the Chronic and Acute Risks of Family Homelessness: Experimental Evidence for Education.

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    Cutuli, J J; Herbers, Janette E

    2018-02-21

    This study considers risk associated with family homelessness for school functioning and experimental evidence on the effects of different housing interventions over time. Students in homeless families (N = 172; M age  = 7.31; SD = 4.15) were randomized to housing interventions that focus on acute risks (community-based rapid rehousing), chronic risks (permanent subsidy), or usual care (UC). A matched group of low-income, housed students served as an additional reference for effects on attendance, school mobility, and reading and math achievement across 4 years. Findings partially support the chronic-risk hypothesis that family homelessness interferes with achievement through its relation to deep poverty. Children randomly assigned to UC perform as well or better than children assigned to housing interventions in this municipality. © 2018 The Authors. Child Development © 2018 Society for Research in Child Development, Inc.

  19. [Chagas disease: clinical aspects and treatment in non-endemic countries].

    Science.gov (United States)

    Le Loup, Guillaume; Lescure, Francois-Xavier; Develoux, Michel; Pialoux, Gilles

    2009-11-01

    International migration has led to the emergence of Chagas disease in industrialized countries, notably France. Clinicians should consider and test for Chagas disease in several situations: chronic cardiac and digestive manifestations in patients who lived (or whose parents lived) in an endemic area; pregnant woman who come from an endemic area and in the infant if the mother's serologic tests are positive; and more rarely, patients with a persistent fever who recently visited an endemic area. During the acute phase, diagnosis is confirmed by parasitological testing. During the chronic phrase, diagnosis remains serologic. The usefulness of PCR has not been determined. The recent recognition of the parasite's pathogenic role during the chronic phase has enlarged the indications for treatment. Today, all patients younger than 50 years with Chagas disease in the acute, chronic symptomatic or chronic asymptomatic phases should receive treatment, except for pregnant women, patients with hepatic or renal failure, or advanced cardiac or digestive manifestations. Treatment must be considered on an individual basis in patients older than 50 years. The frequency and seriousness of potential adverse events due to treatment require careful monitoring of the patient throughout treatment.

  20. Effects of positive end-expiratory pressure on the sigmoid equation in experimental acute lung injury.

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    Bayle, Frederique; Guerin, Claude; Viale, Jean-Paul; Richard, Jean-Christophe; Annat, Guy

    2004-11-01

    To describe inflation and deflation volume-pressure (V-P) curves of the respiratory system by the sigmoidal equation at different levels of positive end-expiratory pressure (PEEP) in acute lung injury. Experimental study. Physiological laboratory in a university setting. Six pigs of 25 kg each. Acute lung injury was induced by oleic acid. PEEP was applied from 0 to 15 cm H(2)O and from 15 to 0 cm H(2)O for 10 min in steps of 5 cmH(2)O. Inflation and deflation V-P curves were constructed from an automated super-syringe that delivers a constant flow of 7 l/min in both inspiratory and expiratory directions. V-P curves were obtained at each level of PEEP without disconnecting the animal from the ventilator. The experimental data were fitted to the sigmoid equation which provided the true inflection point (c), the point of maximal compliance increase (Pmci) reflecting opening/closure and the point of maximal compliance decrease (Pmcd) reflecting end of recruitment/onset of de-recruitment. The sigmoid equation provided an excellent fit. The values of the coefficients of determination were greater than 0.970 (median 0.996, IQR 0.994-0.997 for the 84 determinations). Negative values of Pmci in the deflation limb of the V-P curve were recorded in five pigs, suggesting closure below the volume range studied. Inflation and deflation V-P curves at different PEEPs can be fitted by the sigmoid equation. However, further work is needed to investigate the meaning of negative values for Pmci.

  1. Microdissection studies of the structural alterations induced in rat kidneys by experimental postischemic acute renal failure.

    Science.gov (United States)

    Fetterman, G H; Studnicki, F M; Hashida, Y

    1987-01-01

    A unique opportunity presented itself for a morphologic study of experimental unilateral acute renal failure (ARF) in male rats. The ARF had been induced in the rats by temporary occlusion (1h) of the left renal artery. Twenty-nine rats were divided into subsets as follows: 2-3 h, 24 h, 1 week, 2, 4, 8, and 12 weeks following release of occlusion. Microdissection showed a heterogeneous population of abnormally structured proximal tubules in which the regressive lesions of tubular necrosis were combined with the progressive reaction of repair. The lesions demonstrated are reminiscent of those which have been described in ARF in the human and in experimental animals. Many proximal tubules in the 2- to 3-hour subset presented 1-3 disruptive lesions (DLs) while greater numbers of proximal tubules from the 24-hour group presented 1-5 DLs. Many proximal tubules presented no DLs, but nearly all from the 24-hour subset (97-100%) displayed a squamate appearance which paralleled and was caused by acute tubular necrosis. At 1 week, a dilated pars recta was common, but by this time, the squamate pattern had disappeared. Many casts were present. At 2 weeks, many fewer casts were present in proximal tubules and none were seen at 4, 8 or 12 weeks. The nephrons, particularly the proximal tubules, presented a variety of structural alterations at 2, 4, 8 and 12 weeks. Changes of special interest include (1) the presence of swan-necks; (2) a distinctive squamate appearance of the proximal tubules in the animals killed at 24 h; (3) a spiral, curled appearance caused by differential hyperplasia in animals at 4, 8 and 12 weeks, and (4) a tendency for ischemic lesions to involve all layers of the renal cortex.

  2. Current epidemiological trends for Chagas disease in Latin America and future challenges in epidemiology, surveillance and health policy

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    Álvaro Moncayo

    2009-07-01

    Full Text Available Chagas disease, named after Carlos Chagas, who first described it in 1909, exists only on the American Continent. It is caused by a parasite, Trypanosoma cruzi, which is transmitted to humans by blood-sucking triatomine bugs and via blood transfusion. Chagas disease has two successive phases: acute and chronic. The acute phase lasts six-eight weeks. Several years after entering the chronic phase, 20-35% of infected individuals, depending on the geographical area, will develop irreversible lesions of the autonomous nervous system in the heart, oesophagus and colon, and of the peripheral nervous system. Data on the prevalence and distribution of Chagas disease improved in quality during the 1980s as a result of the demographically representative cross-sectional studies in countries where accurate information was not previously available. A group of experts met in Brasilia in 1979 and devised standard protocols to carry out countrywide prevalence studies on human T. cruzi infection and triatomine house infestation. Thanks to a coordinated multi-country programme in the Southern Cone countries, the transmission of Chagas disease by vectors and via blood transfusion was interrupted in Uruguay in 1997, in Chile in 1999 and in Brazil in 2006; thus, the incidence of new infections by T. cruzi across the South American continent has decreased by 70%. Similar multi-country initiatives have been launched in the Andean countries and in Central America and rapid progress has been reported towards the goal of interrupting the transmission of Chagas disease, as requested by a 1998 Resolution of the World Health Assembly. The cost-benefit analysis of investment in the vector control programme in Brazil indicates that there are savings of US$17 in medical care and disabilities for each dollar spent on prevention, showing that the programme is a health investment with very high return. Many well-known research institutions in Latin America were key elements of a

  3. Correlation between infection rate of triatominies and Chagas Disease in Southwest of Bahia, Brazil: a warning sign?

    Science.gov (United States)

    Silveira, Eliezer A DA; Ribeiro, Israel S; Amorim, Miguel S; Rocha, Dalva V; Coutinho, Helder S; Freitas, Leandro M DE; Tomazi, Laize; Silva, Robson A A DA

    2016-01-01

    Chagas disease, caused by the Trypanosoma cruzi, has a wide distribution in South America, and its main method of control is the elimination of triatomines. It is presented here the geographic distribution and the rate of natural infection by T. cruzi of triatomines collected and evaluated from 2008 to 2013 in southwest of Bahia. Triatomines were captured in the intradomiciliary and peridomiciliary areas of five cities located in the southwest of Bahia state, identified, and analyzed for the presence of trypanosomatids in their feces. During the study period the number of patients suspected for acute Chagas disease was recovered from the Notifiable Diseases Information System (SINAN). 8966 triatomines were captured and identified as belonging to eight species. Twenty-six presented themselves infected, being Triatoma sordida the most abundant and with the highest percentage of infection by T. cruzi. Tremedal was the city with the highest number of cases of acute Chagas' disease reported to SINAN. All cities showed triatomines infected with T. cruzi, so there is considerable risk of vectorial transmission of Chagas disease in the southwestern Bahia state, evidencing the need for vector transmission control programs and preventive surveillance measures.

  4. Respiratory and Systemic Effects of LASSBio596 Plus Surfactant in Experimental Acute Respiratory Distress Syndrome

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    Johnatas Dutra Silva

    2016-02-01

    Full Text Available Background/Aims: Exogenous surfactant has been proposed as adjunctive therapy for acute respiratory distress syndrome (ARDS, but it is inactivated by different factors present in the alveolar space. We hypothesized that co-administration of LASSBio596, a molecule with significant anti-inflammatory properties, and exogenous surfactant could reduce lung inflammation, thus enabling the surfactant to reduce edema and improve lung function, in experimental ARDS. Methods: ARDS was induced by cecal ligation and puncture surgery in BALB/c mice. A sham-operated group was used as control (CTRL. After surgery (6 hours, CTRL and ARDS animals were assigned to receive: (1 sterile saline solution; (2 LASSBio596; (3 exogenous surfactant or (4 LASSBio596 plus exogenous surfactant (n = 22/group. Results: Regardless of exogenous surfactant administration, LASSBio596 improved survival rate and reduced collagen fiber content, total number of cells and neutrophils in PLF and blood, cell apoptosis, protein content in BALF, and urea and creatinine levels. LASSBio596 plus surfactant yielded all of the aforementioned beneficial effects, as well as increased BALF lipid content and reduced surface tension. Conclusion: LASSBio596 exhibited major anti-inflammatory and anti-fibrogenic effects in experimental sepsis-induced ARDS. Its association with surfactant may provide further advantages, potentially by reducing surface tension.

  5. Inhibitory effects of alprazolam on the development of acute experimental autoimmune encephalomyelitis in stressed rats.

    Science.gov (United States)

    Núñez-Iglesias, María J; Novío, Silvia; Almeida-Dias, Antonio; Freire-Garabal, Manuel

    2010-12-01

    The progression and development of multiple sclerosis (MS) has long been hypothesized to be associated with stress. Benzodiazepines have been observed to reduce negative consequences of stress on the immune system in experimental and clinical models, but there are no data on their effects on MS, or experimental autoimmune encephalomyelitis (EAE), a model for human MS. We designed experiments conducted to ascertain whether alprazolam could modify the clinical, histological and neuroendocrine manifestations of acute EAE in Lewis rats exposed to a chronic auditory stressor. EAE was induced by injection of an emulsion of MBP and complete Freund's adjuvant containing Mycobacterium tuberculosis H37Ra. Stress application and treatment with drugs (placebo or alprazolam) were initiated 5days before inoculation and continued daily for the duration of the experiment (days 14 or 34 postinoculation).Our results show significant increases in the severity of neurological signs, the histological lesions of the spinal cord (inflammation), and the corticosterone plasmatic levels in stressed rats compared to those non-stressed ones. Treatment with alprazolam reversed the adverse effects of stress. These findings could have clinical implications in patients suffering from MS treated with benzodiazepines, so besides the psychopharmacological properties of alprazolam against stress, it has beneficial consequences on EAE. Copyright © 2010 Elsevier Inc. All rights reserved.

  6. The Effects of Experimentally Manipulated Social Status on Acute Eating Behavior: A Randomized, Crossover Pilot Study

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    Cardel, MI; Johnson, SL; Beck, J; Dhurandhar, E; Keita, AD; Tomczik, AC; Pavela, G; Huo, T; Janicke, DM; Muller, K; Piff, PK; Peters, JC; Hill, JO; Allison, DB

    2016-01-01

    Both subjective and objectively measured social status has been associated with multiple health outcomes, including weight status, but the mechanism for this relationship remains unclear. Experimental studies may help identify the causal mechanisms underlying low social standing as a pathway for obesity. Our objective was to investigate the effects of experimentally manipulated social status on ad libitum acute dietary intakes and stress-related outcomes as potential mechanisms relating social status and weight. This was a pilot feasibility, randomized, crossover study in Hispanic young adults (n=9; age 19–25; 67% female; BMI ≥18.5 and ≤30 kg/m2). At visit 1, participants consumed a standardized breakfast and were randomized to a high social status position (HIGH) or low social status position (LOW) in a rigged game of Monopoly™. The rules for the game differed substantially in terms of degree of ‘privilege’ depending on randomization to HIGH or LOW. Following Monopoly™, participants were given an ad libitum buffet meal and energy intakes (kcal) were estimated by pre- and post-weighing foods consumed. Stress-related markers were measured at baseline, after the game of Monopoly™, and after lunch. Visit 2 used the same standardized protocol; however, participants were exposed to the opposite social status condition. When compared to HIGH, participants in LOW consumed 130 more calories (p=0.07) and a significantly higher proportion of their daily calorie needs in the ad libitum buffet meal (39% in LOW versus 31% in HIGH; p=0.04). In LOW, participants reported decreased feelings of pride and powerfulness following Monopoly™ (p=0.05) and after their lunch meal (p=0.08). Relative to HIGH, participants in LOW demonstrated higher heart rates following Monopoly™ (p=0.06), but this relationship was not significant once lunch was consumed (p=0.31). Our pilot data suggest a possible causal relationship between experimentally manipulated low social status

  7. Could Carlos Chagas' assumption on the relationship between goiter and chronic Chagas heart disease be correct? A historical reappraisal.

    Science.gov (United States)

    Bestetti, Reinaldo B; Cardinalli-Neto, Augusto; Restini, Carolina B A; Couto, Lucelio B

    2016-01-01

    In 1910, Chagas divided the clinical manifestations of the chronic form of Chagas disease according to heart, Central Nervous System, and thyroid involvement, particularly the presence of goiter. Chagas emphasized the association of goiter with poor houses infested with kissing bugs, the similarity of the clinical picture with that of patients underwent partial thyroidectomy, and with the presence of thyroid sclerosis (inflammation) on histological examination. In addition, Chagas observed that all people living in poor houses infested by sucking bugs had goiter, contrasting with persons who lived in the same region, drinking the same water, but living in good houses, which did not have goiter. Furthermore, Chagas stressed the fact that people without any evidence of thyroid disease that migrated to live in poor houses in areas infested by sucking bugs developed thyroid disease some time later. Finally, and more importantly, Chagas emphasized the association of goiter with cardiac abnormalities in 80% of patients with chronic Chagas heart disease. Despite this, other authors working in different regions did not confirm such an association. A reappraisal of data from a work published in 1949 clearly shows that the presence of goiter was statistically associated with chronic Chagas heart disease and with chronic Chagas disease. Our paper highlights once more the grandiosity of Chagas' work, which has been proved to be correct even in the history of goiter, and justifies our claim for a posthumous Nobel Prize inasmuch as his work was not perceived by the Karolinska Institute. Copyright © 2015. Published by Elsevier Ireland Ltd.

  8. Serodiagnosis of chronic Chagas infection by using EIE-Recombinant-Chagas-Biomanguinhos kit

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    Gomes Yara M

    2001-01-01

    Full Text Available A kit based on an enzyme immunoassay, EIE-Recombinant-Chagas-Biomanguinhos, developed by the Oswaldo Cruz Foundation, was evaluated for the serodiagnosis of chronic Chagas disease. Evaluation was performed with 368 serum samples collected from individuals living in an endemic area for Chagas disease: 131 patients in the chronic phase with confirmed clinical, epidemiological, and serological diagnosis (indirect immunofluorescence, indirect hemagglutination or enzyme-linked immunosorbent assay and 237 nonchagasic seronegative individuals were considered negative control. The EIE-Recombinant-Chagas-Biomanguinhos kit showed high sensitivity, 100% (CI 95%: 96.4-100% and high specificity, 100% (CI 95%: 98-100%. The data obtained were in full agreement with clinical and conventional serology data. In addition, no cross-reaction was observed with sera from patients with cutaneous (n=14 and visceral (n=3 leishmaniasis. However, when these sera were tested by conventional serological assays for Chagas disease, cross-reactions were detected in 14.3% and 33.3% of the patients with cutaneous and visceral leishmaniasis, respectively. No cross-reactions were observed when sera from nonchagasic seronegative patients bearing other infectious disease (syphilis, n=8; HTLV, n=8; HCV, n=7 and HBV, n=12 were tested. In addition, sera of patients with inconclusive results for Chagas disease by conventional serology showed results in agreement with clinical evaluation, when tested by the kit. These results are relevant and indicate that the refered kit provides a safe immunodiagnosis of Chagas disease and could be used in blood bank screening.

  9. Does a spontaneous cure for chagas' disease exist?

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    Rodrigo Zeledón

    1988-03-01

    Full Text Available Six Costa Rican Chagas' disease patients, with wellknown acute phase history and no specific treatment were examined in several occasions during 39, 24, 32, 16 and 14 years, respectively, from the onset. Nome of the patients presented heart abnormalities as revealed by the conventional EKG and ergometry, exceptfor one of them with an incomplete block of the right bundle branch. Also, no alterations of the oesophagus motility was detected manometrically except for another patient who presented a slight hypersensivity reaction to a pharmacological test (Mecholyl. Three out of six patients became serologically negative in 1981, remaining as such until 1986. Besides the conventional serology, the search of protective ("lytic" antibodies was also performed in 1985 and 1986, being completely negative in one of the "cured" patients and dubious in the other two. The hypothesis that these three patients had as spontaneous cure, based on the clinical, serological and parasitologica l findings is discussed.Um grupo de pacientes com doença de Chagas vem sendo acompanhado desde a fase aguda, na Costa Rica, com tempos de evolução entre 14 e 44 anos (mediana de 32 anos. Em todos a doença aguda foi bem comprovada, não sendo realizado tratamento específico em nenhum deles, contra o Trypanosoma cruzi. Todos apresentaram pelo menos uma sorologia positiva ao longo da fase crônica, mas em três deles as técnicas sorológicas convencionais se tomaram parmanentemente negativas em diversos exames ealizados em diferentes laboratórios, entre 1981 e 1986. Nestes três pacientes também a pesquisa de anticorpos líticos foi negativa (um caso ou negativo-duvidosa (dois casos, permanecendo consistentemente positiva nos três outros pacientes com sorologia convencional reagente. Atualmente todos os seis pacientes se apresentam assintomáticos e com xenodiagnóstico negativo. Apenas um deles apresenta distúrbio eletrocardiogràfico mínimo e inespecífico (bloqueio

  10. Assessment of Galectin-3 Polymorphism in Subjects with Chronic Chagas Disease

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    Gabriela da Silva Cruz

    2015-11-01

    Full Text Available AbstractBackground:Galectin-3, a β-galactoside binding lectin, has been described as a mediator of cardiac fibrosis in experimental studies and as a risk factor associated with cardiovascular events in subjects with heart failure. Previous studies have evaluated the genetic susceptibility to Chagas disease in humans, including the polymorphisms of cytokine genes, demonstrating correlations between the genetic polymorphism and cardiomyopathy development in the chronic phase. However, the relationship between the galectin-3 single nucleotide polymorphism (SNP and phenotypic variations in Chagas disease has not been evaluated.Objective:The present study aimed to determine whether genetic polymorphisms of galectin-3 may predispose to the development of cardiac forms of Chagas disease.Methods:Fifty-five subjects with Chagas disease were enrolled in this observational study. Real-time polymerase chain reaction (PCR was used for genotyping the variants rs4644 and rs4652 of the galectin-3 gene.Results:For the SNP rs4644, the relative risk for the cardiac form was not associated with the genotypes AA (OR = 0.79, p = 0.759, AC (OR = 4.38, p = 0.058, or CC (OR = 0.39, p = 0.127. Similarly, for the SNP rs4652, no association was found between the genotypes AA (OR = 0.64, p = 0.571, AC (OR = 2.85, p = 0.105, or CC (OR = 0.49, p = 0.227 and the cardiac form of the disease.Conclusion:Our results showed no association between the different genotypes for both SNPs of the galectin-3 gene and the cardiac form of Chagas disease. (Arq Bras Cardiol. 2015; [online].ahead print, PP.0-0

  11. Correction of Prooxidative-Antioxidative Imbalance after Severe Acute Intoxication (Experimental Study

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    V. A. Myshkin

    2007-01-01

    Full Text Available Objective: to assess the pathological significance of a lipid peroxidation (LPO process after severe intoxications caused by organophosphorous compounds, alcohol, dichloroethane, the efficiency of its correction with the antioxidants pyrimi-dine and benzimidazole derivatives.Materials and methods. The study was conducted on male rats weighing 160—230 g. Models of intoxications with ethanol, dichloroethane, carbofos, armine, or sodium nitrite in the doses causing 30—50% death were employed. LPO products were studied in the lipid extracts of the brain, myocardium, and liver by various methods. The activity of a number of enzymes (catalase, glucose-6-phosphate dehydrogenase, superoxide dismutase, glutathione peroxidase, Na+, K+-ATPase was evaluated in the rats. Serum alanine aminotransferase, aspartate aminotransferase, lactate dehydrogenase, alkaline phosphatase, and acid phosphotase were spectrophotometrically assayed. Quantitative histochemistry was used to determine the activity of succinate dehydrogenase, NAD-diaphorase, and Na+, K+-ATPase. The number of chemical reactions was measured and estimated on a MT-9 TV analyzer microscope. Experimental findings were analyzed by different variation statistical methods using Student’s test.Results. The paper reports the results of comprehensive experimental studies of the efficiency of correction of prooxidative-antioxidative imbalance after severe acute intoxication with chemical prooxidants and some lipophilic xenobiotics. Antioxidants, anti-hypoxants, and actoprotectors, the derivatives of pyrimidine and benzimidazole, were tested.Conclusion. The findings suggest that the immediate sequels of prooxidative-antioxidative imbalance due to experimental intoxications with ethanol, dichloroethane, and organophosphorous compounds are impaired activities of LPO processes, oxidative stress, altered metabolic, bioenergetic processes in organs and tissues. The use hydroxymethyluracil, bemitil, or

  12. Protective human leucocyte antigen haplotype, HLA-DRB1*01-B*14, against chronic Chagas disease in Bolivia.

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    Florencia del Puerto

    Full Text Available BACKGROUND: Chagas disease, caused by the flagellate parasite Trypanosoma cruzi affects 8-10 million people in Latin America. The mechanisms that underlie the development of complications of chronic Chagas disease, characterized primarily by pathology of the heart and digestive system, are not currently understood. To identify possible host genetic factors that may influence the clinical course of Chagas disease, Human Leucocyte Antigen (HLA regional gene polymorphism was analyzed in patients presenting with differing clinical symptoms. METHODOLOGY: Two hundred and twenty nine chronic Chagas disease patients in Santa Cruz, Bolivia, were examined by serological tests, electrocardiogram (ECG, and Barium enema colon X-ray. 31.4% of the examinees showed ECG alterations, 15.7% megacolon and 58.1% showed neither of them. A further 62 seropositive megacolon patients who had undergone colonectomy due to acute abdomen were recruited. We analyzed their HLA genetic polymorphisms (HLA-A, HLA-B, MICA, MICB, DRB1 and TNF-alpha promoter region mainly through Sequence based and LABType SSO typing test using LUMINEX Technology. PRINCIPAL FINDINGS: The frequencies of HLA-DRB1*01 and HLA-B*14:02 were significantly lower in patients suffering from megacolon as well as in those with ECG alteration and/or megacolon compared with a group of patients with indeterminate symptoms. The DRB1*0102, B*1402 and MICA*011 alleles were in strong Linkage Disequilibrium (LD, and the HLA-DRB1*01-B*14-MICA*011 haplotype was associated with resistance against chronic Chagas disease. CONCLUSIONS: This is the first report of HLA haplotype association with resistance to chronic Chagas disease.

  13. Changes in Synovial Fluid Inflammatory Mediators and Cartilage Biomarkers After Experimental Acute Equine Synovitis

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    Wang Guanying

    2015-04-01

    Full Text Available The purpose of the study was to define transient changes in the concentration of inflammatory biomarkers and cartilage biomarkers in the synovial fluid of joints following experimentally induced acute equine synovitis. Acute synovitis was induced in eight skeletally mature mares by a sterile intra-articular injection of 1 mL of phosphate-buffered saline (PBS containing 0.5 ng of lipopolysaccharide (LPS. The solution was injected into the right middle carpal joint. One mL of sterile PBS was injected into the left control joint. Synovial fluid was obtained at the baseline level and at 8, 24, and 168 h after injection. The levels of inflammatory biomarkers-prostaglandin E2 (PGE2, interleukin 1β (IL-1β, and tumour necrosis factor-α (TNF-α, and cartilage turnover biomarkers-collagenase-cleavage neoepitope of type II collagen (C2C and C-terminal crosslinked telopeptide type II collagen (CTX-II were detected with proper assays. Single injections of LPS raised the number of synovial white blood cells and concentrations of total protein, PGE2, IL-1β, TNF-α, C2C, and CTX-II. PGE2 and IL-1β rose sharply at 8 h, while TNF-α increased steadily through 8 h and 24 h, at that point; these three factors returned to the baseline level by 168 h. The time course of C2C and CTX-II concentrations peaked sharply at 24 h, and continued to be significantly elevated over the baseline level even at 168 h. Injections of LPS into the joints led to a temporal inflammatory response, which in turn increased local release of inflammatory biomarkers and significantly altered the concentrations of cartilage markers in the synovial fluid.

  14. Alpha glucocorticoid receptor expression in different experimental rat models of acute lung injury

    NARCIS (Netherlands)

    Bertorelli, Giuseppina; Pesci, Alberto; Peveri, Silvia; Mergoni, Mario; Corradi, Attilio; Cantoni, Anna Maria; Tincani, Giovanni; Bobbio, Antonio; Rusca, Michele; Carbognani, Paolo

    2008-01-01

    Background and objectives: Acute respiratory distress syndrome (ARDS) is a frequent form of hypoxiemic respiratory failure caused by the acute development of diffuse lung inflammation. Dysregulated systemic inflammation with persistent elevation of circulating inflammatory cytokines is the

  15. Flavonoids and Chagas' Disease: The Story So Far!

    Science.gov (United States)

    Nabavi, Seyed Fazel; Sureda, Antoni; Daglia, Maria; Izadi, Morteza; Rastrelli, Luca; Nabavi, Seyed Mohammad

    2017-01-01

    Chagas disease is one of the major health problems in Central and South America, which is caused by the parasitic protozoa, Trypanosoma cruzi. It is commonly transmitted by members of blood-sucking subfamily Triatominae. Chagas disease is associated with cardiac and gastrointestinal manifestations. Up to now, there are no effective vaccines for treatment of Chagas disease and benznidazole and nifurtimox are the only effective anti-Chagas drugs that cause different adverse and side effects. Therefore, much attention has been paid to natural products as novel therapeutic strategies for Chagas disease and its manifestations. Nowadays, some flavonoids could be considered as effective and safe bioactive natural products with potential anti-Chagas activity. Despite the increasing evidence, there is lack of review papers regarding the beneficial effects of flavonoids against Chagas disease and its manifestations. The aim of this paper is to review the available scientific data on the beneficial effects of flavonoids on Chagas disease and its manifestations published over the past two decades. Moreover, we provide an overview on etiology, transmission, epidemiology, clinical manifestations, and current treatment protocols of Chagas disease.

  16. Impact of Global Fxr Deficiency on Experimental Acute Pancreatitis and Genetic Variation in the FXR Locus in Human Acute Pancreatitis

    NARCIS (Netherlands)

    Nijmeijer, R.M.; Schaap, F.G.; Smits, A.J.A.; Kremer, A.E.; Akkermans, L.M.; Kroese, A.B.A.; Rijkers, G.T.; Schipper, M.E.; Verheem, A.; Wijmenga, C.; Gooszen, H.G.; Erpecum, K.J. van

    2014-01-01

    BACKGROUND: Infectious complications often occur in acute pancreatitis, related to impaired intestinal barrier function, with prolonged disease course and even mortality as a result. The bile salt nuclear receptor farnesoid X receptor (FXR), which is expressed in the ileum, liver and other organs

  17. Impact of Global Fxr Deficiency on Experimental Acute Pancreatitis and Genetic Variation in the FXR Locus in Human Acute Pancreatitis

    NARCIS (Netherlands)

    Nijmeijer, Rian M.; Schaap, Frank G.; Smits, Alexander J. J.; Kremer, Andreas E.; Akkermans, Louis M. A.; Kroese, Alfons B. A.; Rijkers, Ger. T.; Schipper, Marguerite E. I.; Verheem, Andre; Wijmenga, Cisca; Gooszen, Hein G.; van Erpecum, Karel J.

    2014-01-01

    Background: Infectious complications often occur in acute pancreatitis, related to impaired intestinal barrier function, with prolonged disease course and even mortality as a result. The bile salt nuclear receptor farnesoid X receptor (FXR), which is expressed in the ileum, liver and other organs

  18. Cognitive impairment in human chronic Chagas' disease.

    Science.gov (United States)

    Mangone, C A; Sica, R E; Pereyra, S; Genovese, O; Segura, E; Riarte, A; Sanz, O P; Segura, M

    1994-06-01

    We proposed to investigate subclinical cognitive impairment secondary to chronic Chagas' disease (CCD). No similar study was previously done. The neuropsychological performance of 45 chronic Chagasic patients and 26 matched controls (age, education place and years of residency in endemic area) was compared using the Mini Mental State Exam (MMSE), Weschler Memory Scale (WMS) and the Weschler Adult Intelligent Scale (WAIS). Non-parametric tests and Chi2 were used to compare group means and multivariate statistics in two way frequency tables for measures of independence and association of categorical variables with the disease. Chagasic patients showed lower MMSE scores (p test p test p < .01) being the digit symbol (p < .03), picture completion (p < .03), picture arrangement (p < .01) and object assembly (p < .03) subtests the most affected. The impairment in non-verbal reasoning, speed of information processing, problem solving, learning and sequencing observed in chronic Chagas disease patients resembles the cognitive dysfunction associated with white matter disease.

  19. [ARCHITECT Chagas(®): a new diagnostic tool in Chagas disease].

    Science.gov (United States)

    Iborra-Bendicho, M Asunción; Albert-Hernández, Miriam; Márquez-Contreras, Carmen; Segovia-Hernández, Manuel

    2012-10-01

    To evaluate a new chemiluminescent microparticle immunoassay (ARCHITECT Chagas(®), Abbott). In this study, 165 samples were tested by two different serological tests. The ARCHITECT Chagas(®) assay was performed using ARCHITECT i2000(SR) system (Abbott). The sensitivity and specificity of ARCHITECT assay was 100% and 96.6%, respectively. The concordance rate was 0.96 (95%CI: 0.92-1) for ELISA and 0.91 (95%CI: 0.85-0.97) for immunofluorescence assay (IFA). The ARCHITECT Chagas(®) assay demonstrates a sensitivity and specificity similar to ELISA and IFA assays; it allows a large volume of samples to be processed with a good standardization and reproducibility, as well as an objective interpretation. Copyright © 2011 Elsevier España, S.L. All rights reserved.

  20. Paraquat poisoning: an experimental model of dose-dependent acute lung injury due to surfactant dysfunction

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    M.F.R. Silva

    1998-03-01

    Full Text Available Since the most characteristic feature of paraquat poisoning is lung damage, a prospective controlled study was performed on excised rat lungs in order to estimate the intensity of lesion after different doses. Twenty-five male, 2-3-month-old non-SPF Wistar rats, divided into 5 groups, received paraquat dichloride in a single intraperitoneal injection (0, 1, 5, 25, or 50 mg/kg body weight 24 h before the experiment. Static pressure-volume (PV curves were performed in air- and saline-filled lungs; an estimator of surface tension and tissue works was computed by integrating the area of both curves and reported as work/ml of volume displacement. Paraquat induced a dose-dependent increase of inspiratory surface tension work that reached a significant two-fold order of magnitude for 25 and 50 mg/kg body weight (P<0.05, ANOVA, sparing lung tissue. This kind of lesion was probably due to functional abnormalities of the surfactant system, as was shown by the increase in the hysteresis of the paraquat groups at the highest doses. Hence, paraquat poisoning provides a suitable model of acute lung injury with alveolar instability that can be easily used in experimental protocols of mechanical ventilation

  1. [Biochemical and functional changes in experimental acute pancreatitis in the rat].

    Science.gov (United States)

    Díez Miralles, M; Pardo Correcher, J M; González Santos, J; Graells Ferrer, M L; Ferrando Marco, J; Regalado Pareja, R I; Medrano Heredia, J

    1989-10-01

    To discover the biochemical alterations occurring in the first 24 hours of acute pancreatitis (PA), we made an experimental study using rats. We used 90 animals in which necrosis and hemorrhage were induced by closing the choledochus. Animals underwent evolutive periods of 1, 2, 3, 4, 5, 6, 12, 18 and 24 hours. They were sacrificed and plasma (to determine amylase, lipase, creatinine and calcium), urine (amylase and creatinine), ascitic and pleural liquid (amylase and lipase) were obtained from 6 animals of each evolutive period. We made a post-mortem study of the pancreas of three animals of each subgroup. There was a significant increase in the amylasemia from the third hour (p less than 0.005) and of plasmatic lipase from the first hour (p less than 0.0001). Creatinine values remained in normal range and calcemia fell after the sixth hour (p less than 0.001). There was an increase in amylase concentration in urine and in ascitic and pleural liquids, and of the lipase in the last two. These changes correlated with the duration of the disease and with the histologic changes of the gland, which consist in edema, acinar necrosis, vasculitis and hemorrhage, which are present from the first hour and increase as time passes.

  2. Contributions of high mobility group box protein in experimental and clinical acute lung injury.

    Science.gov (United States)

    Ueno, Hiroshi; Matsuda, Tomoyuki; Hashimoto, Satoru; Amaya, Fumimasa; Kitamura, Yoshihiro; Tanaka, Masaki; Kobayashi, Atsuko; Maruyama, Ikuro; Yamada, Shingo; Hasegawa, Naoki; Soejima, Junko; Koh, Hidefumi; Ishizaka, Akitoshi

    2004-12-15

    This study was performed to examine the putative role of high mobility group box (HMGB) protein in the pathogenesis of acute lung injury (ALI). Observations were made (1) in 21 patients who were septic with ALI and 15 patients with normal lung function and (2) in a mouse model 24 hours after intratracheal instillation of lipopolysaccharide (LPS). The concentrations of HMGB1 were increased in plasma and lung epithelial lining fluid of patients with ALI and mice instilled with LPS. LPS-induced ALI was mitigated by anti-HMGB1 antibody. Although this protein was not detected in the plasma of control humans or mice, the concentrations of HMGB1 in lung epithelial lining fluid or in bronchoalveolar lavage fluid were unexpectedly high. The nuclear expression of HMGB1 was apparent in epithelial cells surrounding terminal bronchioles in normal mice, whereas its nuclear and cytoplasmic expression was observed in alveolar macrophages in LPS-instilled mice. Lung instillation of HMGB2 did not cause as much inflammation as HMGB1. Extracellular HMGB1 may play a key role in the pathogenesis of clinical and experimental ALI. However, its expression in normal airways is noteworthy and suggests that it also plays a physiologic role in the lung.

  3. Acid-base balance in sheep with experimentally induced acute ruminal lactic acidosis

    Directory of Open Access Journals (Sweden)

    A.F. Sabes

    Full Text Available ABSTRACT This study aimed to investigate the changes in the acid-base balance of sheep with experimentally induced acute ruminal lactic acidosis (ARA. Ten ewes orally received 15 grams of sucrose per kilogram of body mass. Arterial blood samples for blood gas analysis were obtained at the following intervals: before the induction of ARA (control, and 2, 4, 6, 8, 10, 12, 16, 20, 24, 28, 32, 36, 48, 72, 96, 120 and 144 hours after sucrose administration. Urine samples for pH measurement were obtained at the following times: -15 days, -7 days, and immediately before sucrose administration, then at 24, 48, 72, 96, 120 and 144 hours. Thereafter, both blood and urine samples were obtained on the 2nd, 3rd, and 4th following weeks. From 4 hours after the induction, elevation of the pH, bicarbonate and base excess on the arterial blood was observed. After 12 hours, the animals showed a decrease of these parameters, as well as urine acidification, which are symptomatic of metabolic acidosis. Within 28 hours, all parameters were normalized except the base excess, which only returned to normal after 72 hours. Despite the occurrence of acidemia, there was no need for medication and no animals died.

  4. Cell-specific regulation of Ferroportin transcription following experimentally-induced acute anemia in mice.

    Science.gov (United States)

    Chiabrando, Deborah; Fiorito, Veronica; Marro, Samuele; Silengo, Lorenzo; Altruda, Fiorella; Tolosano, Emanuela

    2013-01-01

    Ferroportin (FPN), the sole characterized iron exporter, is mainly controlled by the peptide hormone hepcidin in response to iron, erythroid factors, hypoxia, and inflammation. In addition, intracellular iron level controls FPN translation by modulating the binding of Iron Responsive Proteins at the 5'UTR of FPN mRNA. Recently, hypoxia inducible factor (HIF)2α has been shown to regulate FPN expression in intestinal cells. Here we show that, during experimentally-induced acute anemia in mice, FPN is regulated at transcriptional level in a cell-specific manner. FPN mRNA level increases in duodenum and spleen macrophages, whereas it does not change in liver and is strongly down-regulated in erythroid precursors. These results were confirmed in Caco2, Raw264.7 and K562 cells treated with a hypoxic stimulus. Moreover, we found a differential expression of HIF1α and HIF2α in cells and tissues that might account for the specificity of FPN regulation. Thus, hypoxia, by directly controlling hepcidin and its target FPN, orchestrates a complex regulatory network aimed at ensuring rapid iron recovery from the periphery and efficient iron utilization in the erythroid compartment. Copyright © 2012 Elsevier Inc. All rights reserved.

  5. Passionate love and relationship thinkers: experimental evidence for acute cortisol elevations in women.

    Science.gov (United States)

    Loving, Timothy J; Crockett, Erin E; Paxson, Aubri A

    2009-07-01

    We assessed the impact of an individual difference variable, relationship-focused thinking, on women's acute salivary cortisol responses during and after a guided imagery task. Specifically, 29 healthy women, all of whom were experiencing high levels of passionate love, but varied on levels of relationship-focused thinking, were assigned to one of two experimental conditions: a partner reflection condition or a cross-sex friend reflection condition. Results indicated that women experiencing passionate love evidenced increased cortisol levels when asked to reflect on their romantic partner and relationship relative to women asked to reflect on a cross-sex friendship, but this difference was particularly pronounced and relatively long-lasting for those women characterized by a high amount of relationship-focused thinking. Our study significantly expands extant work on the passionate love-cortisol link by isolating the impact of a specific psychological variable, relationship-focused thinking, on the physiological experience of falling in love. We believe our work highlights the advances that can be made when established work in the close relationships and neuroendocrine fields are integrated.

  6. The subjective experience of acute, experimentally-induced Salvia divinorum inebriation.

    Science.gov (United States)

    Addy, Peter H; Garcia-Romeu, Albert; Metzger, Matthew; Wade, Jenny

    2015-04-01

    This study examined the overall psychological effects of inebriation facilitated by the naturally-occurring plant hallucinogen Salvia divinorum using a double-blind, randomized, placebo-controlled trial. Thirty healthy individuals self-administered Salvia divinorum via combustion and inhalation in a quiet, comfortable research setting. Experimental sessions, post-session interviews, and 8-week follow-up meetings were audio recorded and transcribed to provide the primary qualitative material analyzed here. Additionally, post-session responses to the Hallucinogen Rating Scale provided a quantitative groundwork for mixed-methods discussion. Qualitative data underwent thematic content analysis, being coded independently by three researchers before being collaboratively integrated to provide the final results. Three main themes and 10 subthemes of acute intoxication emerged, encompassing the qualities of the experience, perceptual alterations, and cognitive-affective shifts. The experience was described as having rapid onset and being intense and unique. Participants reported marked changes in auditory, visual, and interoceptive sensory input; losing normal awareness of themselves and their surroundings; and an assortment of delusional phenomena. Additionally, the abuse potential of Salvia divinorum was examined post hoc. These findings are discussed in light of previous research, and provide an initial framework for greater understanding of the subjective effects of Salvia divinorum, an emerging drug of abuse. © The Author(s) 2015.

  7. Closed-chest experimental porcine model of acute myocardial infarction-reperfusion.

    Science.gov (United States)

    Pérez de Prado, Armando; Cuellas-Ramón, Carlos; Regueiro-Purriños, Marta; Gonzalo-Orden, J Manuel; Pérez-Martínez, Claudia; Altónaga, José R; García-Iglesias, M José; Orden-Recio, M Asunción; García-Marín, Juan F; Fernández-Vázquez, Felipe

    2009-01-01

    Progress in cardiovascular regenerative medicine research requires the availability of appropriate experimental animal models that are as close to humans as feasible. Our objective was to assess the validity of a porcine endovascular model of myocardial infarction and reperfusion. Fifteen domestic pigs (Large White race) were anesthetized and pre-medicated with amiodarone. Endovascular fluoroscopy-guided coronary procedures were performed to occlude the mid-left anterior descending artery using a coronary angioplasty balloon. Occlusion was confirmed by angiography and electrocardiography. After 75 min the balloon catheter system was withdrawn and the presence of reperfusion flow was verified. The animals were sacrificed after 1 and 2 weeks of follow-up, the hearts were explanted, and the extent of myocardial infarction with respect to the left ventricle was quantified. Overall survival rate was 67%. Five animals died prematurely: 3 showing signs of heart failure, 1 had reperfusion failure (final TIMI flow grade 1) and 1 succumbed to acute stress. The most common adverse event was ventricular fibrillation (87% of the animals) and defibrillation was effective in all affected animals. The extent of myocardial infarct in the animals followed-up for 1 and 2 weeks was similar (20.4+/-4.3% vs. 20.9+/-2.8%, respectively; p=0.8) but was significantly greater in the animals that died prematurely (29.5+/-3.6%, p=0.02). The endovascular porcine model we have explored constitutes a feasible and reproducible alternative for the evaluation of human myocardial infarction and reperfusion.

  8. Looking for combination of benznidazole and Trypanosoma cruzi-triosephosphate isomerase inhibitors for Chagas disease treatment

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    Elena Aguilera

    Full Text Available BACKGROUND The current chemotherapy for Chagas disease is based on monopharmacology with low efficacy and drug tolerance. Polypharmacology is one of the strategies to overcome these limitations. OBJECTIVES Study the anti-Trypanosoma cruzi activity of associations of benznidazole (Bnz with three new synthetic T. cruzi-triosephosphate isomerase inhibitors, 2, 3, and 4, in order to potentiate their actions. METHODS The in vitro effect of the drug combinations were determined constructing the corresponding isobolograms. In vivo activities were assessed using an acute murine model of Chagas disease evaluating parasitaemias, mortalities and IgG anti-T. cruzi antibodies. FINDINGS The effect of Bnz combined with each of these compounds, on the growth of epimastigotes, indicated an additive action or a synergic action, when combining it with 2 or 3, respectively, and an antagonic action when combining it with 4. In vivo studies, for the two chosen combinations, 2 or 3 plus one fifth equivalent of Bnz, showed that Bnz can also potentiate the in vivo therapeutic effects. For both combinations a decrease in the number of trypomastigote and lower levels of anti-T. cruzi IgG-antibodies were detected, as well clear protection against death. MAIN CONCLUSIONS These results suggest the studied combinations could be used in the treatment of Chagas disease.

  9. [Possible oral transmission of Chagas disease among hydrocarbons sector workers in Casanare, Colombia, 2014].

    Science.gov (United States)

    Zuleta-Dueñas, Liliana Patricia; López-Quiroga, Ángela Johana; Torres-Torres, Fernando; Castañeda-Porras, Oneida

    2017-06-01

    Trypanosoma cruzi, the etiological agent for Chagas disease, can be transmitted by oral intake of contaminated food or drinks. During epidemiological week 14 of 2014, two cases of acute Chagas disease were notified among hydrocarbons sector workers in Paz de Ariporo, Casanare. To characterize the affected population, to establish control and prevention measures and to confirm the outbreak. We conducted an outbreak investigation that included the following components: a) Search for symptomatic people compatible with Chagas disease according to the case definition for their referral to medical services; b) entomological survey (192/197 houses); c) sanitary inspection and microbiological analysis of food samples; and d) study of reservoirs. Data management and analysis were done with Epi-Info 7.1.5 using descriptive statistics. We also calculated intradomicile and peridomicile triatomine infestation indexes. We detected 552 exposed people; 40 had the disease (7.2%), of whom seven were women (17,5%) and 33, men (82.5%), i.e., a male-female ratio of 5:1. The mean age was 39.1 ± 10.8 years; the attack rate was 7.2% and lethality, 5% (2/40). Symptoms included fever (100% of cases), headache (80%), myalgia and arthralgia (65%), facial edema (55%), and abdominal pain (37.5%). The mean incubation time was 17 days (range: 3-21). Rhodnius prolixus domiciliary infestation index was 3.3 % and 2.2% in the peridomicile. In the five restaurants inspected sanitary conditions were deficient and food samples were microbiologically non-conforming. We found a dog and two opossums positive for IgG antibodies by ELISA. Environmental, sanitary and epidemiological conditions at the place confirmed an outbreak of Chagas diseases related to occupational exposure, possibly by oral transmission, which may be the largest to date in Colombia.

  10. Experimental researches on acute toxicity of a Bidens tripartita extract in mice - preliminary investigations.

    Science.gov (United States)

    Sandu, R B; Tarţău, L; Miron, A; Zagnat, M; Ghiciuc, C M; Lupuşoru, C E

    2012-01-01

    Plants take up an important place in traditional medicine and scientific research confirmed properties about their use as alternative therapy. Bidens tripartita, commonly known as Three-lobe Beggarticks, Three-part Beggarticks, Trifid Bur-marigold, is a flowering plant in the genus Bidens, family Compositae, subfamily Asteroideae. Evaluation of the chemical composition of this plant has revealed the presence of flavonoids, xanthophylls, volatile oil, acetylene and polyacetylene, sterols, aurones, chalcones, caffeine and tannins. Theoretical data investigation regarding Bidens tripartita plant and experimental researches on acute toxicity of an original extract in mice. The vegetal product of Bidens tripartita used for study was obtained by maceration and extraction in alcohol, and its chemical composition was determined. Acute toxicity of the alcoholic extract of Bidens tripartita was assessed by median lethal dose (LD50) calculation, using a limit dose test of up- and- down procedure at a limit dose of 2000mg/kbw after intraperitoneal administration in mice. In the alcoholic extract of Bidens tripartita different active principles were identified: tannins, anthracene derivatives, triterpenes, coumarins, antocyanosides. The toxicity of plant product was evaluated by different characteristic signs for the mouse which can be retained as toxicity elements of the extract. Using the intraperitoneal route, the animals showed dose-dependent signs of toxicity, ranging from lack of appetite, depression, immobility and respiratory distress to death. Single-dose intraperitoneal LD50 value of the alcoholic Bidens tripartita extract in mice was 4038 mg/kg. No macroscopic changes were seen in the organs of mice that died following extract administration. Histopathological lesions were not found in all examined organs. The obtained LD50 value classifies the study plant extract as slightly toxic according to Hodge and Sterner toxicity scale. We determined the low toxic dose at a

  11. Remote ischemic perconditioning attenuates acute inflammation of experimental musculocutaneous flaps following ischemia-reperfusion injury.

    Science.gov (United States)

    Krag, Andreas E; Eschen, Gete T; Damsgaard, Tine E; Svaerdborg, Mille; Steiniche, Torben; Kiil, Birgitte J

    2017-02-01

    In free flap reconstruction and replantation surgery, prolonged ischemia time may lead to flap or replantation failure. The aim of the study was to investigate the effects of hypothermic flap ischemia or remote ischemic perconditioning (RIPER) during normothermic ischemia on acute inflammation of musculocutaneous flaps subjected to ischemia-reperfusion injury. In 24 pigs, a musculocutaneous latissimus dorsi flap was dissected and subjected to 4 hours of arterial ischemia and 7 hours of reperfusion. The animals were allocated into two experimental groups: hypothermic flap ischemia at 4°C (n = 8) or normothermic flap ischemia with RIPER (n = 8), and one control group with normothermic flap ischemia (n = 8). The hypothermic ischemic flaps were cooled in a basin with fresh water and ice. RIPER was initiated 1 hour before reperfusion, by inducing three 10 min cycles of hind limb ischemia with a tourniquet, each separated by 10 min of reperfusion. Acute inflammation was described by inflammatory cytokine secretion (IL-1β, IL-6, IL-10, IL-12p40, and TNF-α) from the flap during reperfusion, and by quantitative determination of macrophages in flap biopsies of dermis, subcutaneous tissue, and skeletal muscle following reperfusion. No significant differences were found between normothermic and hypothermic flap ischemia in inflammatory cytokine secretion. However, the IL-6 secretion was significantly reduced in the RIPER group compared with the control group at 5 hours of reperfusion (P = 0.036), and in the RIPER group compared with the hypothermic ischemia group at 3 (P = 0 0.0063), 5 (P = 0.0026), and 7 hours of reperfusion (P = 0.028). The IL-12p40 secretion was significantly reduced in the RIPER group compared with the control group (P = 0.0054) as well as the hypothermic ischemia group (P = 0.028) at 5 hours of reperfusion. No significant difference was found among groups in macrophage infiltration. RIPER reduced IL-6 and IL-12p40 secretion

  12. Relationship between neutrophil-mediated oxidative injury during acute experimental pyelonephritis and chronic renal scarring.

    OpenAIRE

    Meylan, P R; Markert, M; Bille, J; Glauser, M P

    1989-01-01

    Previous experiments with rats have suggested that pyelonephritic scarring after acute ascending Escherichia coli pyelonephritis partly results from excessive polymorphonuclear leukocyte (PMN) infiltration and activation in the kidney parenchyma. We have studied the role of PMN oxidative metabolism in generating tissue injury during acute pyelonephritis. Rats with acute pyelonephritis were treated with dapsone (25 mg/kg twice daily for 3 days), a compound known to prevent PMN oxidant damage. ...

  13. Chagas disease: what is known and what is needed - A background article

    Directory of Open Access Journals (Sweden)

    José Rodrigues Coura

    2007-10-01

    Full Text Available Chagas disease began millions of years ago as an enzootic disease of wild animals and started to be transmitted to man accidentally in the form of an anthropozoonosis when man invaded wild ecotopes. Endemic Chagas disease became established as a zoonosis over the last 200-300 years through forest clearance for agriculture and livestock rearing and adaptation of triatomines to domestic environments and to man and domestic animals as a food source. It is estimated that 15 to 16 million people are infected with Trypanosoma cruzi in Latin America and 75 to 90 million people are exposed to infection. When T. cruzi is transmitted to man through the feces of triatomines, at bite sites or in mucosa, through blood transfusion or orally through contaminated food, it invades the bloodstream and lymphatic system and becomes established in the muscle and cardiac tissue, the digestive system and phagocytic cells. This causes inflammatory lesions and immune responses, particularly mediated by CD4+, CD8+, interleukin-2 (IL and IL-4, with cell and neuron destruction and fibrosis, and leads to blockage of the cardiac conduction system, arrhythmia, cardiac insufficiency, aperistalsis, and dilatation of hollow viscera, particularly the esophagus and colon. T. cruzi may also be transmitted from mother to child across the placenta and through the birth canal, thus causing abortion, prematurity, and organic lesions in the fetus. In immunosuppressed individuals, T. cruzi infection may become reactivated such that it spreads as a severe disease causing diffuse myocarditis and lesions of the central nervous system. Chagas disease is characterized by an acute phase with or without symptoms, and with entry point signs (inoculation chagoma or Romaña's sign, fever, adenomegaly, hepatosplenomegaly, and evident parasitemia, and an indeterminate chronic phase (asymptomatic, with normal results from electrocardiogram and x-ray of the heart, esophagus, and colon or with a

  14. [Experimental rationale for the use of enterosorbents in acute ethanol intoxication].

    Science.gov (United States)

    Orbidans, A G; Terekhin, G A; Vladimirskiĭ, E V; Terekhina, N A

    2009-01-01

    The experiment on 83 rats has provided a rationale for the use of enterosorbents in acute ethanol intoxication. Polysorb reduces the halflife of ethanol, recovers physical fitness in the animals with acute poisoning. The enterosorbents polysorb, litovit, and sapropel have been found to have a corrective effect on the level of the major plasma antioxidant ceruloplasmin in acute ethanol intoxication. Enterosorbents are an effective detoxifying agent in this condition. Examining the mechanisms of toxic action of ethanol allows the most expedient treatment policy to be substantiated in acute poisonings.

  15. Molecular epidemiologic source tracking of orally transmitted Chagas disease, Venezuela.

    Science.gov (United States)

    Segovia, Maikell; Carrasco, Hernán J; Martínez, Clara E; Messenger, Louisa A; Nessi, Anaibeth; Londoño, Juan C; Espinosa, Raul; Martínez, Cinda; Alfredo, Mijares; Bonfante-Cabarcas, Rafael; Lewis, Michael D; de Noya, Belkisyolé A; Miles, Michael A; Llewellyn, Martin S

    2013-07-01

    Oral outbreaks of Chagas disease are increasingly reported in Latin America. The transitory presence of Trypanosoma cruzi parasites within contaminated foods, and the rapid consumption of those foods, precludes precise identification of outbreak origin. We report source attribution for 2 peri-urban oral outbreaks of Chagas disease in Venezuela via high resolution microsatellite typing.

  16. [Nifurtimox, a bright future for treatment of Chagas disease].

    Science.gov (United States)

    Wolf, A; Boulliat, C; Coillot, C; Rouault, M; Gaillard, K; Beranger, C; Oliver, M

    2011-04-01

    Nifurtimox is one of the two molecules used for treatment of Chagas disease. Although posology has not yet been clearly defined, nifurtimox is increasingly used, especially in combination with eflonithin. Nifurtimox is perfectly suited to the WHO's Chagas disease eradication program.

  17. Changing patterns of acute phase proteins and inflammatory mediators in experimental caprine coccidiosis.

    Science.gov (United States)

    Hashemnia, Mohammad; Khodakaram-Tafti, Azizollah; Razavi, Seyed Mostafa; Nazifi, Saeed

    2011-09-01

    This experiment was conducted to assess the changing patterns and relative values of acute phase proteins and inflammatory cytokines in experimental caprine coccidiosis. Eighteen newborn kids were allocated to 3 equal groups. Two groups, A and B, were inoculated with a single dose of 1×10(3) and1×10(5) sporulated oocysts of Eimeria arloingi, respectively. The third group, C, received distilled water as the control. Blood samples were collected from the jugular vein of each kid in both groups before inoculation and at days 7, 14, 21, 28, 35, and 42 post-inoculation (PI), and the levels of haptoglobin (Hp), serum amyloid A (SAA), TNF-α, and IFN-γ were measured. For histopathological examinations, 2 kids were selected from each group, euthanized, and necropsied on day 42 PI. Mean Hp concentrations in groups A and B (0.34 and 0.68 g/L) at day 7 PI were 3.2 and 6.3 times higher than the levels before inoculation. The mean SAA concentrations in groups A and B (25.6 and 83.5 µg/ml) at day 7 PI were 4.2 and 13.7 times higher than the levels before inoculation. The magnitude and duration of the Hp and SAA responses correlated well with the inoculation doses and the severity of the clinical signs and diarrhea in kids. These results were consistent with the histopathological features, which showed advanced widespread lesions in group B. In both groups, significant correlations were observed for TNF-α and IFN-γ with SAA and Hp, respectively. In conclusion, Hp and SAA can be useful non-specific diagnostic indicators in caprine coccidiosis.

  18. The antiulcer effect of Cibotium barometz leaves in rats with experimentally induced acute gastric ulcer

    Directory of Open Access Journals (Sweden)

    AL-Wajeeh NS

    2017-03-01

    Full Text Available Nahla Saeed Al-Wajeeh,1 Maryam Hajrezaie,1 Nawal Al-Henhena,1 Sareh Kamran,1 Elham Bagheri,1 Maryam Zahedifard,1 Kamelia Saremi,1 Suzita Mohd Noor,1 Hapipah Mohd Ali,2 Mahmood Ameen Abdulla11Department of Biomedical Science, Faculty of Medicine, 2Department of Chemistry, Faculty of Science, University of Malaya, Kuala Lumpur, MalaysiaAbstract: Cibotium barometz is a pharmaceutical plant customarily used in traditional medicine in Malaysia for the treatment of different diseases, such as gastric ulcer. The gastroprotective effect of C. barometz leaves against ethanol-induced gastric hemorrhagic abrasions in Sprague Dawley rats has been evaluated in terms of medicinal properties. Seven groups of rats (normal control and ulcerated control groups, omeprazole 20 mg/kg, 62.5, 125, 250, and 500 mg/kg of C. barometz correspondingly were used in antiulcer experiment and pretreated with 10% Tween 20. After 1 hour, the normal group was orally administered 10% Tween 20, whereas absolute alcohol was fed orally to ulcerated control, omeprazole, and experimental groups. Gastric’s homogenate were assessed for endogenous enzymes activities. Stomachs were examined macroscopically and histologically. Grossly, the data demonstrated a significant decrease in the ulcer area of rats pretreated with plant extract in a dose-dependent manner with respect to the ulcerated group. Homogenates of the gastric tissue exhibited significantly increased endogenous enzymes activities in rats pretreated with C. barometz extract associated with the ulcerated control group. Histology of rats pretreated with C. barometz extract group using hematoxylin and eosin staining exhibited a moderate-to-mild disruption of the surface epithelium with reduction in submucosal edema and leucocyte infiltration in a dose-dependent manner. In addition, it showed heat shock protein70 protein up-expression and BCL2-associated X protein downexpression. These outcomes might be attributed to the

  19. Experimental model for acute kidney injury caused by uropathogenic Escherichia coli

    Directory of Open Access Journals (Sweden)

    Beata Skowron

    2017-06-01

    Full Text Available Introduction: Acute kidney injury (AKI is the rapid deterioration of renal function, diagnosed on the basis of an increase in serum creatinine and abnormal urinary parameters. AKI is associated with increased risk of mortality or chronic kidney disease (CKD.The aim of the study was to develop an experimental model for AKI resulting from Escherichia coli-induced pyelonephritis. E. coli was isolated from a patient with clinical symptoms of urinary tract infection (UTI.Material/Methods: The study included three groups of female Wistar rats (groups 1, 2 and 3, in which pyelonephritis was induced by transurethral inoculation with highly virulent E. coli (105, 107 and 109 cfu/ml, respectively. Urine and blood samples for analysis were obtained prior to the inoculation (day 0, as well as 7, 14 and 21 days thereafter.Results: Aside from a microbiological examination of urine samples, daily urine output, serum creatinine (CreaS, creatinine clearance (CrCl, interleukin 6 (IL-6, fractional excretion of sodium (FENa and fractional excretion of urea (FEUrea were determined. A histopathological examination of kidney and urinary bladder specimens was conducted as well. While UTI-related pyelonephritis developed irrespective of E. coli inoculum size, AKI was observed only following transurethral administration of E. coli at the intermediate and high dose, i.e. 107 and 109 cfu/ml, respectively (group 2 and 3. Discussion: An increase in CreaS and abnormal diuresis were accompanied by changes in parameters specific for various forms of AKI, i.e. FENa and FEUrea. Based on these changes, administration of E. coli at 107 cfu/ml was demonstrated to induce renal AKI, whereas inoculation with 109 cfu/ml seemed to cause not only ascending pyelonephritis, but perhaps also bacteremia and urosepsis (prerenal component of AKI.

  20. Definition and drivers of acute traumatic coagulopathy: clinical and experimental investigations

    DEFF Research Database (Denmark)

    Frith, Christopher Donald; Goslings, J C; Gaarder, C

    2010-01-01

    Acute traumatic coagulopathy (ATC) is an impairment of hemostasis that occurs early after injury and is associated with a 4-fold higher mortality, increased transfusion requirements and organ failure.......Acute traumatic coagulopathy (ATC) is an impairment of hemostasis that occurs early after injury and is associated with a 4-fold higher mortality, increased transfusion requirements and organ failure....

  1. [The history of Chagas' disease in Argentina: conceptual, institutional, and political evolution].

    Science.gov (United States)

    Zabala, Juan Pablo

    2009-07-01

    In the one hundred years since the identification of Chagas disease, major changes have occurred in its scientific conception, institutional recognition, and political weight. From a medical perspective, it was seen as the cause of goiter, next its acute effects were emphasized, and then its effects on cardiac health received greater attention. In similar fashion, sanitary policy first downplayed the disease's importance, then elevated it to the role of a national cause, and gradually relegated it to the bottom of the agenda. The article briefly presents the key points of this historical trajectory in Argentina, exploring the cognitive, political, and institutional underpinnings of the disease as both a social and biological fact.

  2. Description of an oral Chagas disease outbreak in Venezuela, including a vertically transmitted case.

    Science.gov (United States)

    Noya, Belkisyolé Alarcón de; Pérez-Chacón, Gladymar; Díaz-Bello, Zoraida; Dickson, Sonia; Muñoz-Calderón, Arturo; Hernández, Carlos; Pérez, Yadira; Mauriello, Luciano; Moronta, Eyleen

    2017-08-01

    We describe the eleventh major outbreak of foodborne Trypanosoma cruzi transmission in urban Venezuela, including evidence for vertical transmission from the index case to her fetus. After confirming fetal death at 24 weeks of gestation, pregnancy interruption was performed. On direct examination of the amniotic fluid, trypomastigotes were detected. T. cruzi specific-polymerase chain reaction (PCR) also proved positive when examining autopsied fetal organs. Finally, microscopic fetal heart examination revealed amastigote nests. Acute orally transmitted Chagas disease can be life threatening or even fatal for pregnant women and unborn fetuses owing to vertical transmission. There is therefore an urgent need to improve national epidemiologic control measures.

  3. Experimentally induced acute uric acid nephropathy in rabbits: Findings of high resolution gray scale and doppler ultrasonographies

    Energy Technology Data Exchange (ETDEWEB)

    Yang, Ik; Chung, Soo Young; Lee, Kyung Won; Kim, Hong Dae; Ko, Eun Young; Won, Mi Sook; Noh, Jung Woo [Hallym University College of Medicine, Seoul (Korea, Republic of); Park, Moon Hyang [Hanyang University College of Medicine, Seoul (Korea, Republic of)

    2001-12-15

    To evaluate changes of the high-resolution (HR) gray scale and doppler ultrasonographic (US) characteristics of experimentally induced acute uric acid (UA) nephropathy in rabbits. Acute UA nephropathy was induced in ten rabbits using supersaturated lithium carbonate solution. The rabbits were divided in two groups. Group I consisted of five rabbits, and they were injected with a single dose of 150 ml of saturated UA over one hour. During tis period, serial US studies of the kidneys of these rabbits were performed every ten minutes. Group II consisted of the remaining five rabbits, and three injections of 50 ml of saturated UA solution were given on the first, fifth and eight day and follow-up was done upto twenty fifth day. Sequential HR and Doppler US, renal biopsy and blood sampling were performed on day 1, 5, 8, 21, and 25 in the group II rabbits. In group I, HR and Doppler US examination revealed the normal resistive index without significant abnormality. On the other hand, US studies of group II showed poor renal corticomedullary differentiation, decreased renal blood flow and elevated resistive index. There was statistically significant correlation among US findings, histologic characteristics and chemical index (BUN, creatinine) of renal function. In addition, sequentially increased size and volume of the kidney were noted in both groups. HR gray scale and doppler US characteristics of experimentally induced acute UA nephropathy in rabbits were similar to those of acute renal failure caused by other well-known causes.

  4. Myocardial repolarization dispersion and autonomic nerve activity in a canine experimental acute myocardial infarction model.

    Science.gov (United States)

    Piccirillo, Gianfranco; Moscucci, Federica; D'Alessandro, Gaetana; Pascucci, Matteo; Rossi, Pietro; Han, Seongwook; Chen, Lan S; Lin, Shien-Fong; Chen, Peng-Sheng; Magrì, Damiano

    2014-01-01

    Evidence from a canine experimental acute myocardial infarction (MI) model shows that until the seventh week after MI, the relationship between stellate ganglion nerve activity (SGNA) and vagal nerve activity (VNA) progressively increases. The purpose of this study was to evaluate how autonomic nervous system activity influences temporal myocardial repolarization dispersion at this period. We analyzed autonomic nerve activity as well as QT and RR variability from recordings previously obtained in nine dogs. From a total of 48 short-term ECG segments, 24 recorded before and 24 recorded 7 weeks after experimentally-induced MI, we obtained three indices of temporal myocardial repolarization dispersion: QTe (from Q-wave to T-wave end), QTp (from Q-wave to T-wave peak), and Te (from T-wave peak to T-wave end) variability index (QTeVI, QTpVI, TeVI). We also performed heart rate variability power spectral analysis on the same segments. After MI, all the QT variables increased QTeVI (median [interquartile range]) (from -1.76[0.82] to -1.32[0.68]), QTeVI (from -1.90[1.01] to -1.45[0.78]), and TeVI (from -0.72[0.67] to -0.22[1.00]), whereas all RR spectral indices decreased (P <.001 for all). Distinct circadian rhythms in QTeVI (P <.05,) QTpVI (P <.001) and TeVI (P <.05) appeared after MI with circadian variations resembling that of SGNA/VNA. The morning QTpVI and TeVI acrophases approached the SGNA/VNA acrophase. Conversely, the evening QTeVI acrophase coincided with another SGNA/VNA peak. After MI, regression analysis detected a positive relationship between SGNA/VNA and TeVI (R(2): 0.077; β: 0.278; p< 0.001). Temporal myocardial repolarization dispersion shows a circadian variation after MI reaching its peak at a time when sympathetic is highest and vagal activity lowest. © 2013 Heart Rhythm Society Published by Heart Rhythm Society All rights reserved.

  5. Cannabinoid HU210 Protects Isolated Rat Stomach against Impairment Caused by Serum of Rats with Experimental Acute Pancreatitis

    Science.gov (United States)

    Cao, Ming-hua; Li, Yong-yu; Xu, Jing; Feng, Ya-jing; Lin, Xu-hong; Li, Kun; Han, Tong; Chen, Chang-Jie

    2012-01-01

    Acute pancreatitis (AP), especially severe acute pancreatitis often causes extra-pancreatic complications, such as acute gastrointestinal mucosal lesion (AGML) which is accompanied by a considerably high mortality, yet the pathogenesis of AP-induced AGML is still not fully understood. In this report, we investigated the alterations of serum components and gastric endocrine and exocrine functions in rats with experimental acute pancreatitis, and studied the possible contributions of these alterations in the pathogenesis of AGML. In addition, we explored the intervention effects of cannabinoid receptor agonist HU210 and antagonist AM251 on isolated and serum-perfused rat stomach. Our results showed that the AGML occurred after 5 h of AP replication, and the body homeostasis was disturbed in AP rat, with increased levels of pancreatic enzymes, lipopolysaccharide (LPS), proinflammtory cytokines and chemokines in the blood, and an imbalance of the gastric secretion function. Perfusing the isolated rat stomach with the AP rat serum caused morphological changes in the stomach, accompanied with a significant increment of pepsin and [H+] release, and increased gastrin and decreased somatostatin secretion. HU210 reversed the AP-serum-induced rat pathological alterations, including the reversal of transformation of the gastric morphology to certain degree. The results from this study prove that the inflammatory responses and the imbalance of the gastric secretion during the development of AP are responsible for the pathogenesis of AGML, and suggest the therapeutic potential of HU210 for AGML associated with acute pancreatitis. PMID:23285225

  6. Effect of Glucocorticoids on Ultrastructure of Myocardial Muscle in the Course of Experimentally Induced Acute Myocardial Ischemia

    Directory of Open Access Journals (Sweden)

    Piotr Kuropka

    2017-01-01

    Full Text Available The search for effective methods of myocardial cytoprotection against ischemia is the most significant issue in modern cardiology and cardiac surgery. Glucocorticoids are deemed very strong modulators of inflammatory response and thus can potentially protect heart muscle from postreperfusion injury and myocardial ischemia during cardiac surgery. Ultrastructural examination of the left ventricle heart samples revealed that the intravenous application of dexamethasone and hydrocortisone proved to exert cytoprotective effect on cardiomyocytes during experimentally induced acute ischemia in rats.

  7. The impact of Chagas disease control in Latin America: a review

    Directory of Open Access Journals (Sweden)

    JCP Dias

    2002-07-01

    Full Text Available Discovered in 1909, Chagas disease was progressively shown to be widespread throughout Latin America, affecting millions of rural people with a high impact on morbidity and mortality. With no vaccine or specific treatment available for large-scale public health interventions, the main control strategy relies on prevention of transmission, principally by eliminating the domestic insect vectors and control of transmission by blood transfusion. Vector control activities began in the 1940s, initially by means of housing improvement and then through insecticide spraying following successful field trials in Brazil (Bambui Research Centre, with similar results soon reproduced in São Paulo, Argentina, Venezuela and Chile. But national control programmes only began to be implemented after the 1970s, when technical questions were overcome and the scientific demonstration of the high social impact of Chagas disease was used to encourage political determination in favour of national campaigns (mainly in Brazil. Similarly, large-scale screening of infected blood donors in Latin America only began in the 1980s following the emergence of AIDS. By the end of the last century it became clear that continuous control in contiguous endemic areas could lead to the elimination of the most highly domestic vector populations - especially Triatoma infestans and Rhodnius prolixus - as well as substantial reductions of other widespread species such as T. brasiliensis, T. sordida, and T. dimidiata, leading in turn to interruption of disease transmission to rural people. The social impact of Chagas disease control can now be readily demonstrated by the disappearance of acute cases and of new infections in younger age groups, as well as progressive reductions of mortality and morbidity rates in controlled areas. In economic terms, the cost-benefit relationship between intervention (insecticide spraying, serology in blood banks and the reduction of Chagas disease (in terms

  8. Early double-negative thymocyte export in Trypanosoma cruzi infection is restricted by sphingosine receptors and associated with human chagas disease.

    Directory of Open Access Journals (Sweden)

    Ailin Lepletier

    2014-10-01

    Full Text Available The protozoan parasite Trypanosoma cruzi is able to target the thymus and induce alterations of the thymic microenvironmental and lymphoid compartments. Acute infection results in severe atrophy of the organ and early release of immature thymocytes into the periphery. To date, the pathophysiological effects of thymic changes promoted by parasite-inducing premature release of thymocytes to the periphery has remained elusive. Herein, we show that sphingosine-1-phosphate (S1P, a potent mediator of T cell chemotaxis, plays a role in the exit of immature double-negative thymocytes in experimental Chagas disease. In thymuses from T. cruzi-infected mice we detected reduced transcription of the S1P kinase 1 and 2 genes related to S1P biosynthesis, together with increased transcription of the SGPL1 sphingosine-1-lyase gene, whose product inactivates S1P. These changes were associated with reduced intrathymic levels of S1P kinase activity. Interestingly, double-negative thymocytes from infected animals expressed high levels of the S1P receptor during infection, and migrated to lower levels of S1P. Moreover, during T. cruzi infection, this thymocyte subset expresses high levels of IL-17 and TNF-α cytokines upon polyclonal stimulation. In vivo treatment with the S1P receptor antagonist FTY720 resulted in recovery the numbers of double-negative thymocytes in infected thymuses to physiological levels. Finally, we showed increased numbers of double-negative T cells in the peripheral blood in severe cardiac forms of human Chagas disease.

  9. Rapid and widely disseminated acute phase protein response after experimental bacterial infection of pigs

    DEFF Research Database (Denmark)

    Skovgaard, Kerstin; Mortensen, Shila; Boye, Mette

    2009-01-01

    The acute phase protein response is a well-described generalized early host response to tissue injury, inflammation and infection, observed as pronounced changes in the concentrations of a number of circulating serum proteins. The biological function of this response and its interplay with other...... infection in pigs. The lung infection was established with the pig specific respiratory pathogen Actinobacillus pleuropneumoniae. Quantitative real-time PCR based expression analysis were performed on samples from liver, tracheobronchial lymph node, tonsils, spleen and on blood leukocytes, supplemented...... with measurements of interleukin-6 and selected acute phase proteins in serum. C-reactive protein and serum amyloid A were clearly induced 14-18 h after infection. Extrahepatic expression of acute phase proteins was found to be dramatically altered as a result of the lung infection with an extrahepatic acute phase...

  10. Association between probiotics and enteral nutrition in an experimental acute pancreatitis model in rats

    NARCIS (Netherlands)

    Baal, M.C.P.M. van; Rens, M.J. van; Geven, C.B.; Pol, F.M. van de; Brink, I. van den; Hannink, G.J.; Nagtegaal, I.D.; Peters, W.H.M.; Rijkers, G.T.; Gooszen, H.G.

    2014-01-01

    BACKGROUND/OBJECTIVES: Recently, a randomized controlled trial showed that probiotic prophylaxis was associated with an increased mortality in enterally fed patients with predicted severe pancreatitis. In a rat model for acute pancreatitis, we investigated whether an association between probiotic

  11. Binding of the ligand [3H]MK-801 to the MK-801 binding site of the N-methyl-D-aspartate receptor during experimental encephalopathy from acute liver failure and from acute hyperammonemia in the rabbit

    NARCIS (Netherlands)

    R.J. de Knegt (Robert); J. Kornhuber (Johannes); S.W. Schalm (Solko); K. Rusche (K.); P.F. Riederer (Peter); J. Tan (J.)

    1993-01-01

    textabstractBinding of the ligand [3H]MK-801 to the MK-801 binding site of the N-methyl-D-aspartate (NMDA) receptor population on brain homogenates in rabbits was studied during experimental encephalopathy from acute liver failure and from acute hyperammonemia in the rabbit. Homogenates were

  12. Chagas disease, a risk factor for high blood pressure.

    Science.gov (United States)

    Vicco, Miguel Hernán; Rodeles, Luz; Yódice, Agustina; Marcipar, Iván

    2014-12-01

    Chagas disease is a parasite infection caused by the protozoan Trypanosoma cruzi. Its most common complications is chronic Chagas heart disease but impairments of the systemic vasculature also has been observed. Although the different mechanisms that regulate blood pressure are disrupted, to our knowledge data on the association of hypertension and chronic Chagas disease are scarce. In this regard we evaluate whether Chagas disease constitutes a high blood pressure risk factor. We recruited 200 individuals, half of them with positive serology for T. cruzi. They were subjected to a complete clinical examination. The mean age of sampled individuals was 46.7 ± 12.3, and the mean of systolic and diastolic blood pressure were 124 ± 12 mmHg and 82 ± 10 mmHg, respectively. There were no between-group differences regarding age, sex distribution or body mass index. Chagas disease contributed significantly to high blood pressure (OR = 4, 95% CI 1.8323-7.0864, p = 0.0002). Our results reveal an important association between Chagas disease and high blood pressure, which should be contemplated by physicians in order to promote preventive cardiovascular actions in patients with Chagas disease.

  13. A global systematic review of Chagas disease prevalence among migrants.

    Science.gov (United States)

    Conners, Erin E; Vinetz, Joseph M; Weeks, John R; Brouwer, Kimberly C

    2016-04-01

    Human migration has been identified as a potential factor for increased Chagas disease risk and has transformed the disease from a Latin American problem to a global one. We conducted a systematic review of the scientific literature between 2004-2014 in order to: summarize recent seroprevalence estimates of Chagas disease among Latin American migrants, in both endemic and non-endemic settings; compare seroprevalence estimates in migrants to countrywide prevalence estimates; and identify risk factors for Chagas disease among migrants. A total of 320 studies were screened and 23 studies were included. We found evidence that the prevalence of Chagas disease is higher than expected in some migrant groups and that reliance on blood donor screening prevalence estimates underestimates the burden of disease. Overall there is a dearth of high quality epidemiologic studies on the prevalence of Chagas disease in migrants, especially among intra-regional migrants within Latin America. Given that this zoonotic disease cannot likely be eradicated, improved surveillance and reporting is vital to continuing control efforts. More accurate health surveillance of both Latin American migrants and the Chagas disease burden will help countries appropriately scale up their response to this chronic disease. Overall, improved estimates of Chagas disease among migrants would likely serve to highlight the real need for better screening, diagnostics, and treatment of individuals living with the disease. Copyright © 2016 Elsevier B.V. All rights reserved.

  14. Association between probiotics and enteral nutrition in an experimental acute pancreatitis model in rats.

    Science.gov (United States)

    van Baal, Mark C; van Rens, Michiel J; Geven, Christopher B; van de Pol, Francien M; van den Brink, Ilona W; Hannink, Gerjon; Nagtegaal, Iris D; Peters, Wilbert H; Rijkers, Ger T; Gooszen, Hein G

    2014-01-01

    Recently, a randomized controlled trial showed that probiotic prophylaxis was associated with an increased mortality in enterally fed patients with predicted severe pancreatitis. In a rat model for acute pancreatitis, we investigated whether an association between probiotic prophylaxis and enteral nutrition contributed to the higher mortality rate. Male Sprague-Dawley rats were allocated to four groups: 1) acute pancreatitis (n = 9), 2) acute pancreatitis and probiotic prophylaxis (n = 10), 3) acute pancreatitis and enteral nutrition (n = 10), and 4) acute pancreatitis, probiotic prophylaxis and enteral nutrition (n = 11). Acute pancreatitis was induced by intraductal glycodeoxycholate and intravenous cerulein infusion. Enteral nutrition, saline, probiotics and placebo were administered through a permanent jejunal feeding. Probiotics or placebo were administered starting 4 days before induction of pancreatitis and enteral nutrition 1 day before start until the end of the experiment, 6 days after induction of pancreatitis. Tissue samples and body fluids were collected for microbiological and histological examination. In all animals, serum amylase was increased six hours after induction of pancreatitis. After fulfilling the experiment, no differences between groups were found in histological severity of pancreatitis, degree of discomfort, weight loss, histological examination of small bowel and bacterial translocation (all p > 0.05). Overall mortality was 10% without differences between groups (p = 0.54). No negative association was found between prophylactic probiotics and enteral nutrition in acute pancreatitis. No new clues for a potential mechanism responsible for the higher mortality and bowel ischaemia in the PROPATRIA study were found. Copyright © 2014 IAP and EPC. Published by Elsevier B.V. All rights reserved.

  15. The Open Lung Approach Improves Pulmonary Vascular Mechanics in an Experimental Model of Acute Respiratory Distress Syndrome.

    Science.gov (United States)

    Santos, Arnoldo; Lucchetta, Luca; Monge-Garcia, M Ignacio; Borges, Joao Batista; Tusman, Gerardo; Hedenstierna, Goran; Larsson, Anders; Suarez-Sipmann, Fernando

    2017-03-01

    To test whether positive end-expiratory pressure consistent with an open lung approach improves pulmonary vascular mechanics compared with higher or lower positive end-expiratory pressures in experimental acute respiratory distress syndrome. Experimental study. Animal research laboratory. Ten pigs, 35 ± 5.2 kg. Acute respiratory distress syndrome was induced combining saline lung lavages with injurious mechanical ventilation. The positive end-expiratory pressure level resulting in highest compliance during a decremental positive end-expiratory pressure trial after lung recruitment was determined. Thereafter, three positive end-expiratory pressure levels were applied in a random order: hyperinflation, 6 cm H2O above; open lung approach, 2 cm H2O above; and collapse, 6 cm H2O below the highest compliance level. High fidelity pressure and flow sensors were placed at the main pulmonary artery for measuring pulmonary artery resistance (Z0), effective arterial elastance, compliance, and reflected pressure waves. After inducing acute respiratory distress syndrome, Z0 and effective arterial elastance increased (from 218 ± 94 to 444 ± 115 dyn.s.cm and from 0.27 ± 0.14 to 0.62 ± 0.22 mm Hg/mL, respectively; p mechanics compared with higher or lower positive end-expiratory pressure settings.

  16. Effect of platelet-activating factor antagonist WEB 2086 on microcirculatory disorders in acute experimental pancreatitis of graded severity.

    Science.gov (United States)

    Mann, Oliver; Tiefenbacher, Wolf-Jonas; Kaifi, Jussuf; Schneider, Claus; Kluth, Dirk; Bloechle, Christian; Yekebas, Emre; Izbicki, Jakob R; Strate, Tim

    2009-01-01

    Platelet-activating factor (PAF) is an important mediator of inflammation and postulated to be involved in the pathogenesis of acute pancreatitis. In this study, we evaluated the therapeutic effect of PAF antagonist WEB 2086 in acute experimental pancreatitis of graded severity in rats. According to a block design, 64 animals were randomly allocated to 8 groups. Severe necrotizing pancreatitis was induced by intraductal infusion of taurocholic acid (4%, 0.4 mL), and the combination of glycodeoxycholic acid (10 mmol/L, 1.0 mL/kg, intraductal infusion) and cerulein (5 microg/kg per hour, intravenous) was applied to induce intermediate pancreatitis, or cerulein alone (5 microg/kg per hour, intravenous) to establish edematous pancreatitis. WEB 2086 was given 15 minutes after beginning the induction of pancreatitis. Pancreatic microcirculation was analyzed in vivo with an epiluminescent microscope. Histopathology was evaluated by a validated score. Trypsinogen-activating peptide and serum amylase were analyzed sequentially. WEB 2086 had no significant influence on the breakdown of microcirculation, leukocyte adherence, histopathological damage, and amylase levels in severe necrotizing pancreatitis, intermediate pancreatitis, and edematous pancreatitis. Only in intermediate pancreatitis was there a significant reduction of trypsinogen-activating peptide levels. In our study, PAF antagonist WEB 2086 had no beneficial effect on microcirculation in acute experimental pancreatitis.

  17. Cognitive impairment in human chronic Chagas' disease

    Directory of Open Access Journals (Sweden)

    C.A. Mangone

    1994-06-01

    Full Text Available We proposed to investigate subclinical cognitive impairment secondary to chronic Chagas' disease (CCD. No similar study was previously done. The neuropsychological performance of 45 chronic Chagasic patients and 26 matched controls (age, education place and years of residency in endemic area was compared using the Mini Mental State Exam (MMSE, Weschler Memory Scale (WMS and the Weschler Adult Intelligent Scale (WAIS. Non-parametric tests and Chi2 were used to compare group means and multivariate statistics in two way frequency tables for measures of independence and association of categorical variables with the disease. Results: Chagasic patients showed lower MMSE scores (p<004, poor orientation (p<.004, and attention (p<.007. Lower WMS MQ were associated with CCD (Chi2 5.9; p<.01; Fisher test p<.02. Lower WAIS IQ were associated with CCD (Chi2 6.3, p<.01; Fisher test p<.01 being the digit symbol (p<.03, picture completion (p<.03, picture arrangement (p<.01 and object assembly (p<.03 subtests the most affected. The impairment in non-verbal reasoning, speed of information processing, problem solving, learning and sequencing observed in chronic Chagas disease patients resembles the cognitive dysfunction associated with white matter disease.

  18. Chagas disease: changes in knowledge and management.

    Science.gov (United States)

    Lescure, François-Xavier; Le Loup, Guillaume; Freilij, Hector; Develoux, Michel; Paris, Luc; Brutus, Laurent; Pialoux, Gilles

    2010-08-01

    More than 100 years after the discovery of human American trypanosomiasis by Carlos Chagas, our knowledge and management of the disease are profoundly changing. Substantial progress made by disease control programmes in most endemic areas contrasts with persisting difficulties in the Gran Chaco region in South America and the recent emergence of the disease in non-endemic areas because of population movements. In terms of pathogenesis, major discoveries have been made about the life cycle and genomics of Trypanosoma cruzi, and the role of the parasite itself in the chronic phase of the disease. From a clinical perspective, a growing number of arguments have challenged the notion of an indeterminate phase, and suggest new approaches to manage patients. New methods such as standardised PCR will be necessary to ensure follow-up of this chronic infection. Although drugs for treatment of Chagas disease are limited, poorly tolerated, and not very effective, treatment indications are expanding. The results of the Benznidazole Evaluation For Interrupting Trypanosomiasis (BENEFIT) trial in 2012 will also help to inform treatment. Mobilisation of financial resources to fund research on diagnosis and randomised controlled trials of treatment are international health priorities. 2010 Elsevier Ltd. All rights reserved.

  19. Update in treatment of Chagas disease.

    Science.gov (United States)

    Le Loup, Guillaume; Pialoux, Gilles; Lescure, François Xavier

    2011-10-01

    This review discusses the recent data about the pathogenesis of Chagas disease, tolerance of drugs, and follow-up of patients impacting the treatment of Chagas disease in immunocompetent and immunocompromised patients. The role of the parasite to promote direct or indirect organ damage in the chronic phase of the disease as well as the usefulness of antiparasitic treatment to slow or prevent the deterioration of cardiac function and the aggravation of Chagasic cardiomyopathy lead to an extension of the indications of treatment. Tolerance is poor for the two drugs, benznidazole and nifurtimox. The rates of adverse events and treatment discontinuation before 60 days are higher with nifurtimox. PCR, and in the near future immunologic tests, might allow assessment of the early success or failure of the antiparasitic treatment. Assessment of alternative drugs, such as posaconazole, and of new strategies of treatment (combination of two antiparasitic drugs, association of antiparasitic and immunomodulatory drugs, and re-treatment), and follow-up are a global health priority.

  20. [The third and new face of Chagas disease].

    Science.gov (United States)

    Pays, J-F

    2016-08-01

    After the publication of the results of the BENEFIT study concluding that the benznidazole (5 mg/kg/d/60 d) is ineffective to stop the progression of the established Chagas' cardiomyopathy in adults, the author evokes the new experiences and the new challenges of 2016 regarding Chagas disease while speculating on its future and by calling back some elements little known of his history, in particular the fact that it is Chagas who invented about it to some extent the concept of "neglected disease".

  1. Enfermedad de Chagas o Tripanosomiasis Americana.

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    Felipe Guhl

    2000-08-01

    Full Text Available

    Situación Actual de Colombia.

    La enfermedad de Chagas o tripanosomiasis americana es una enfermedad parasitaria crónica causada por un protozoario flagelado el Trypanosoma cruzi, descrito por primera vez por Carlos Chagas, médico brasileño, a comienzos de este siglo y en su honor se denominó la enfermedad que lleva su nombre.

    Este parásito normalmente se transmite al ser humano a través de insectos triatomíneos estrictamente hematófagos de la familia Reduviidae, en el momento en que perforan la piel para succionar la sangre que los alimenta.

    Sin embargo, no se inocula directamente por intermedio de las estructuras bucales del insecto en el momento de la picadura como en el caso de las tripanosomiasis africanas, si no que se deposita pasivamente en la piel a través de las heces del insecto, penetrando en el cuerpo por la herida que causa la picadura u otras abrasiones de la piel o de la mucosa. El T. cruzi, también puede transmitirse por infección congénita, por transfusión de sangre contaminada o por el transplante de órganos contaminados. El ciclo vital del parásito es largo y complejo y su desarrollo tiene varias etapas, tanto en el vector triatomineo como en el huésped vertebrado .

    La Enfermedad de Chagas constituye una amenaza permanente para casi la cuarta parte de toda la población de América Latina. Si bien la enfermedad se encuentra presente en toda América Central y del Sur, sus manifestaciones y características epidemiológicas son altamente variables entre una y otra zona endémica. Existe una gran diversidad en las tasas de prevalencia, formas de transmisión, características parasitarias, patología clínica, vectores y reservorios.

    Más que cualquier otra enfermedad parasitaria, la enfermedad de Chagas se relaciona con el desarrollo económico y social de la población: los insectos triatomineos y las enfermedades que ellos transmiten existirán mientras en

  2. Trypanosoma cruzi: correlation of muscle lesions with contractile properties in the acute phase of experimental infection in mice (Mus musculus).

    Science.gov (United States)

    Ramirez-Archila, Mario V; Muñiz, Jesús; Virgen-Ortiz, Adolfo; Newton-Sánchez, Oscar; Melnikov, Valery G; Dobrovinskaya, Oxana R

    2011-08-01

    Parasitism in skeletal muscles and myositis are commonly observed during experimental Trypanosoma cruzi infection. The effect of T. cruzi infection on contractile properties of skeletal muscles in consecutive periods of the acute infection in BALB/c mice was studied. Albarrada strain (clone 4) which was isolated in Mexico and has demonstrated a high level of blood parasitemia and parasitism in skeletal muscles was used. Isolated strips of rectus abdominis muscle were subjected to direct electrical field in vitro. Alternatively, plantaris muscles were stimulated in situ through the sciatic nerve. The peak amplitudes of a single twitch and tetanus contractions were considered to estimate the mechanical properties of muscles. Histopathological analysis was performed to correlate functional changes with the evolution of tissue parasitism and tissue injury. Contractile properties of muscles were significantly attenuated during acute T. cruzi infection. The percentage of damaged muscles rather than the character of tissue pathology affected their contractile properties significantly. Copyright © 2011 Elsevier Inc. All rights reserved.

  3. Current and developing therapeutic agents in the treatment of Chagas disease.

    Science.gov (United States)

    Apt, Werner

    2010-09-24

    Chagas disease must be treated in all its stages: acute, indeterminate, chronic, and initial and middle determinant chronic, due to the fact that DNA of the parasite can be demonstrated by PCR in chronic cases, where optical microscopy does not detect parasites. Nifurtimox (NF) and benznidazole (BNZ) are the drugs accepted to treat humans based upon ethical considerations and efficiency. However, both the drugs produce secondary effects in 30% of the cases, and the treatment must be given for at least 30-60 days. Other useful drugs are itraconazole and posaconazole. The latter may be the drug to treat Chagas disease in the future when all the investigations related to it are finished. At present, there is no criterion of cure for chronic cases since in the majority, the serology remains positive, although it may decrease. In acute cases, 70% cure with NF and 75% with BNZ is achieved. In congenital cases, 100% cure is obtained if the treatment is performed during the first year of life. In chronic acquired cases, 20% cure and 50% improvement of the electrocardiographic changes are obtained with itraconazole.

  4. Acquired non-Chagas megacolon associated with the use of psychiatric medication: case report and differential diagnosis with Chagas megacolon Megacólon adquirido não chagásico associado ao uso de medicação psiquiátrica: relato de caso e diagnóstico diferencial com megacólon chagásico

    Directory of Open Access Journals (Sweden)

    Sheila Jorge Adad

    2008-06-01

    Full Text Available A case of acquired megacolon in a 62-year-old man with acute abdomen due to sigmoid volvulus is reported. The case was associated with the use of psychiatric medications. The aim in this report was to emphasize the differential diagnosis with Chagas megacolon. Anatomopathological examination did not show any evidence of denervation, ganglionitis and/or myositis, and the serological test for Chagas disease was negative.Relata-se caso de megacólon adquirido, associado ao uso de medicamentos psiquiátricos, em homem de 62 anos, com abdome agudo por volvo de sigmóide, com o objetivo de destacar o diagnóstico diferencial de megacólon chagásico. O exame anátomo-patológico não evidenciou denervação, ganglionite e/ou miosite e a sorologia para doença de Chagas foi negativa.

  5. Management of gastrostomy to prevent perforation in acute severe corrosive esophagitis and gastritis: an experimental study.

    Science.gov (United States)

    Han, Serdar; Han, Ünsal; Atinkaya, Cansel; Osmanoğlu, Gökhan; Cavuşoğlu, Tarık; Dıkmen, Erkan

    2011-01-01

    Symptomatic treatment is still the most commonly preferred treatment modality for acute severe esophagitis and gastritis. Clinical results of this treatment range from pathologies like stricture formation to loss of life. In our study, we aimed to demonstrate the effect of immediate gastrostomy in preventing perforation due to corrosive trauma. We used 32 rats in two study groups. In Group I (n: 16 rats), 1 ml of corrosive agent (10% NaOH solution) was administered and immediate gastrostomies were performed within 2 hours. In Group II (n: 16 rats), 1 ml corrosive agent (10% NaOH solution) was administered and the rats were treated symptomatically; no operation was performed. Acute death was observed in 5 rats just after the corrosive agent was administered at the beginning of the study. Three rats from Group II died due to esophageal and gastric perforation within one week (25%). Necrosis was reported in 5 non-gastrostomized rats; however, no necrosis was observed in the gastrostomized group (p=0.037). Severe acute corrosive esophagitis and gastritis may be fatal. Furthermore, survivors may suffer from lifelong associated problems. From this study, we concluded that immediate gastrostomy in acute corrosive esophagitis and gastritis may play an important role in preventing necrosis and perforation risk.

  6. Evaluation of Propranolol Effect on Experimental Acute and Chronic Toxoplasmosis Using Quantitative PCR

    Science.gov (United States)

    Montazeri, Mahbobeh; Ebrahimzadeh, Mohammad Ali; Ahmadpour, Ehsan; Sharif, Mehdi; Sarvi, Shahabeddin

    2016-01-01

    Current therapies against toxoplasmosis are limited, and drugs have significant side effects and low efficacies. We evaluated the potential anti-Toxoplasma activity of propranolol at a dose of 2 or 3 mg/kg of body weight/day in vivo in the acute and chronic phases. Propranolol as a cell membrane-stabilizing agent is a suitable drug for inhibiting the entrance of Toxoplasma gondii tachyzoites into cells. The acute-phase assay was performed using propranolol, pyrimethamine, and propranolol plus pyrimethamine before (pretreatment) and after (posttreatment) intraperitoneal challenge with 1 × 103 tachyzoites of the virulent T. gondii strain RH in BALB/c mice. Also, in the chronic phase, treatment was performed 12 h before intraperitoneal challenge with 1 × 106 tachyzoites of the virulent strain RH of T. gondii in rats. One week (in the acute phase) and 2 months (in the chronic phase) after postinfection, tissues were isolated and DNA was extracted. Subsequently, parasite load was calculated using quantitative PCR (qPCR). In the acute phase, in both groups, significant anti-Toxoplasma activity was observed using propranolol (P toxoplasmosis. Also, propranolol combined with pyrimethamine reduced the parasite load as well as significantly increased survival of mice in the pretreatment group. In the chronic phase, anti-Toxoplasma activity and decreased parasite load in tissues were observed with propranolol. In conclusion, the presented results demonstrate that propranolol, as an orally available drug, is effective at low doses against acute and latent murine toxoplasmosis, and the efficiency of the drug is increased when it is used in combination therapy with pyrimethamine. PMID:27645234

  7. American Trypanosomiasis (Also Known as Chagas Disease) Triatomine Bug FAQs

    Science.gov (United States)

    ... Article (Transfusion — March 8, 2012): The United States Trypanosoma cruzi Infection Study: Evidence for Vector-borne Transmission of ... of reduviid bug that can carry the parasite Trypanosoma cruzi that causes Chagas disease. Various triatomine bugs in ...

  8. American Trypanosomiasis (Also Known as Chagas Disease) Detailed FAQs

    Science.gov (United States)

    ... Article (Transfusion — March 8, 2012): The United States Trypanosoma cruzi Infection Study: Evidence for Vector-borne Transmission of ... disease? Chagas disease is caused by the parasite Trypanosoma cruzi , which is transmitted to animals and people by ...

  9. 2 nd Brazilian Consensus on Chagas Disease, 2015.

    Science.gov (United States)

    Dias, João Carlos Pinto; Ramos, Alberto Novaes; Gontijo, Eliane Dias; Luquetti, Alejandro; Shikanai-Yasuda, Maria Aparecida; Coura, José Rodrigues; Torres, Rosália Morais; Melo, José Renan da Cunha; Almeida, Eros Antonio de; Oliveira, Wilson de; Silveira, Antônio Carlos; Rezende, Joffre Marcondes de; Pinto, Fabiane Scalabrini; Ferreira, Antonio Walter; Rassi, Anis; Fragata, Abílio Augusto; Sousa, Andréa Silvestre de; Correia, Dalmo; Jansen, Ana Maria; Andrade, Glaucia Manzan Queiroz; Britto, Constança Felícia De Paoli de Carvalho; Pinto, Ana Yecê das Neves; Rassi, Anis; Campos, Dayse Elisabeth; Abad-Franch, Fernando; Santos, Silvana Eloi; Chiari, Egler; Hasslocher-Moreno, Alejandro Marcel; Moreira, Eliane Furtado; Marques, Divina Seila de Oliveira; Silva, Eliane Lages; Marin-Neto, José Antonio; Galvão, Lúcia Maria da Cunha; Xavier, Sergio Salles; Valente, Sebastião Aldo da Silva; Carvalho, Noêmia Barbosa; Cardoso, Alessandra Viana; Silva, Rafaella Albuquerque E; Costa, Veruska Maia da; Vivaldini, Simone Monzani; Oliveira, Suelene Mamede; Valente, Vera da Costa; Lima, Mayara Maia; Alves, Renato Vieira

    2016-12-01

    Chagas disease is a neglected chronic condition with a high burden of morbidity and mortality. It has considerable psychological, social, and economic impacts. The disease represents a significant public health issue in Brazil, with different regional patterns. This document presents the evidence that resulted in the Brazilian Consensus on Chagas Disease. The objective was to review and standardize strategies for diagnosis, treatment, prevention, and control of Chagas disease in the country, based on the available scientific evidence. The consensus is based on the articulation and strategic contribution of renowned Brazilian experts with knowledge and experience on various aspects of the disease. It is the result of a close collaboration between the Brazilian Society of Tropical Medicine and the Ministry of Health. It is hoped that this document will strengthen the development of integrated actions against Chagas disease in the country, focusing on epidemiology, management, comprehensive care (including families and communities), communication, information, education, and research .

  10. Melatonin in Chagas´ disease: Possible therapeutic value La melatonina en la enfermedad de Chagas: Su posible valor terapéutico

    Directory of Open Access Journals (Sweden)

    Daniel P. Cardinali

    2011-10-01

    Full Text Available Chagas' disease is a severe health problem in Latin America, causing approximately 50 000 deaths a year, with approximately 18 million infected people. About 25-30% of the patients infected with Trypanosoma cruzi develop the chronic form of the disease. The protective response against T. cruzi depends on both innate and acquired immunity involving macrophages, natural killer cells, T and B lymphocytes, and the production of proinflammatory Th-1 cytokines. In addition, an increased nitric oxide (NO production in macrophages leading to effective microbicidal action is needed to control parasitemia. Melatonin is detectable in T. cruzi and may play a role in promoting infection whereas, when administered in high doses during the acute phase of T. cruzi infection, it can decrease parasitemia while reducing NO production. During chronic disease progression, the sustained oxidative stress concomitant to myocardial damage could be reduced by administering melatonin. It is hypothesized that the coordinated administration of a melatonin agonist like the MT1/MT2 agonist ramelteon, that lacks antioxidant activity and may not affect NO production during the acute phase, and of melatonin in doses high enough to decrease oxidative damage, to preserve mitochondrial and to prevent cardiomyopathy during the chronic phase, could be a novel add-on treatment of Chagas´ disease.La enfermedad de Chagas es un problema grave de salud en América Latina, causando cerca de 50 000 muertes al año y unos 18 millones de infectados. Alrededor del 25-30% de los pacientes infectados con Trypanosoma cruzi desarrollan la forma crónica de la enfermedad. La respuesta de defensa ante el T. cruzi depende de la inmunidad innata y adquirida con la participación de macrófagos, células “natural killer”, linfocitos T y B, y la producción de citoquinas proinflamatorias de tipo Th-1. Además, el aumento en la producción de óxido nítrico (NO en los macrófagos lleva a una acci

  11. Epidemiology of Chagas disease in Ecuador. A brief review

    OpenAIRE

    Aguilar V, H Marcelo; Abad-Franch, Fernando; Racines V, José; Paucar C, Aura

    1999-01-01

    Chagas disease is a complex public health problem that has been underestimated in Ecuador. Here we review the relevant published information, and present unpublished and new data that help to understand the current Chagas disease epidemiological situation and its evolution in the country. Three main characteristics have been identified: (i) persistence of Trypanosoma cruzi transmission in already known foci; (ii) a marked endemicity in some urban areas of Guayaquil; and (iii) the transformati...

  12. A Multi-disciplinary Overview of Chagas in Periurban Peru

    Directory of Open Access Journals (Sweden)

    Sarah McCune

    2010-04-01

    Full Text Available There are between 8 and 11 million cases of America Human Trypanosomiasis, commonly known as Chagas disease, in Latin America. Chagas is endemic in southern Peru, especially the Arequipa region, where it has expanded from poor, rural areas to periurban communities. This paper summarizes the findings of four studies in periurban Arequipa: on determinants of disease-vector infestation; on prevalence, spatial patterns, and risk factors of Chagas; on links between migration, settlement patterns, and disease-vector infestation; and on the relationship between discordant test results and spatially clustered transmission hotspots. These studies identified two risk factors associated with the disease: population dynamics and the urbanization of poverty. Understanding the disease within this new urban context will allow for improved public health prevention efforts and policy initiatives. Discovered in 1909 by Brazilian physician Carlos Chagas, American Human Trypanosomiasis is a chronic and potentially life-threatening illness found throughout Latin America (Moncayo, 2003. Indeed, it is estimated that there are between 8 and 11 million cases in Mexico and Central and South America (Centers for Disease Control [CDC], 2009. Chagas disease, as it is most commonly known, is endemic in southern Peru, especially in the region of Arequipa. Once thought to be limited to poor, rural areas, the disease is now appearing in the periurban communities that surround Arequipa City, the capital of the region (Cornejo del Carpio, 2003. Understanding the urbanization of Chagas disease will allow public health and medical professionals to better combat the further transmission of the disease. After providing an overview of Chagas and introducing the scope of the disease in Latin America, this paper will summarize the findings of four recent studies conducted in periurban districts in Arequipa. Ultimately, this paper seeks to identify the risk factors associated with Chagas

  13. Irradiated T. cruzi and resistant consomic animals can be useful in Chagas disease studies

    Energy Technology Data Exchange (ETDEWEB)

    Dias, Viviane Liotti; Passos, Luiz Augusto Correa; Salgado, Andreia Ruis [Universidade Estadual de Campinas, SP (Brazil). Centro Multidisciplinar para a Investigacao Biologica (CEMIB/UNICAMP)], e-mail: viviliotti@cemib.unicamp.br; Spencer, Patrick Jack; Nascimento, Nanci do [Instituto de Pesquisas Energeticas e Nucleares (IPEN-CNEN/SP), Sao Paulo, SP (Brazil)

    2009-07-01

    Human Chagas disease is considered the most significant parasitic disease in Latin America. It is estimated that 16-18 million people are infected by T. cruzi. As a consequence, approximately 50,000 deaths occur every year. The acute infection usually goes unrecognized and enters into a chronic stage that persists throughout the host's life span. However, roughly 30% of infected individuals eventually will develop disease with an array of possible manifestations affecting the heart, the digestive tract, and/or the peripheral nervous system. This disease is commonly modeled in inbred mice even though mouse strains used to simulate experimental infection vary considerably. In this way, Wrightsman and Trischmann showed that chromosome 17 was directly involved in a T. cruzi resistance, showing the influence of host's genetic constitution on disease severity. Additionally, in 2003, Passos and Graefe, working separately, quantified parasite burdens in resistant and susceptible strains and applied a backcross strategy to map the genomic loci linked to susceptibility and resistance in inbred mice. The genomes of the animals were scanned with microsatellite markers and the results found by these authors showed that the resistance mechanism is polygenic and is under the control of a complex network. In the particular case of Y strain, in vivo assays indicated that survival was related to the chromosomes 7,11,14,17 and 19. In order to evaluate the influence of each isolated chromosome as well as their interactions, we employed susceptible isogenic mice to construct consomic lineages for each one of those chromosomes. The consomic strains were injected with irradiated and native forms of Y strain T. cruzi, and the infectivity parameters were evaluated by quantitative methods. Radiation caused inability of trypanosomes to infect and kill mice, when these parasites were irradiated with 1 kGy of gamma rays from a {sup 60}Co source. In this experiment we used 10{sup 1

  14. Acute, subacute and long-term subjective effects of psilocybin in healthy humans: a pooled analysis of experimental studies.

    Science.gov (United States)

    Studerus, Erich; Kometer, Michael; Hasler, Felix; Vollenweider, Franz X

    2011-11-01

    Psilocybin and related hallucinogenic compounds are increasingly used in human research. However, due to limited information about potential subjective side effects, the controlled medical use of these compounds has remained controversial. We therefore analysed acute, short- and long-term subjective effects of psilocybin in healthy humans by pooling raw data from eight double-blind placebo-controlled experimental studies conducted between 1999 and 2008. The analysis included 110 healthy subjects who had received 1-4 oral doses of psilocybin (45-315 µg/kg body weight). Although psilocybin dose-dependently induced profound changes in mood, perception, thought and self-experience, most subjects described the experience as pleasurable, enriching and non-threatening. Acute adverse drug reactions, characterized by strong dysphoria and/or anxiety/panic, occurred only in the two highest dose conditions in a relatively small proportion of subjects. All acute adverse drug reactions were successfully managed by providing interpersonal support and did not need psychopharmacological intervention. Follow-up questionnaires indicated no subsequent drug abuse, persisting perception disorders, prolonged psychosis or other long-term impairment of functioning in any of our subjects. The results suggest that the administration of moderate doses of psilocybin to healthy, high-functioning and well-prepared subjects in the context of a carefully monitored research environment is associated with an acceptable level of risk.

  15. [Modification of proteins in the course of oxidative stress in acute experimental pancreatitis].

    Science.gov (United States)

    Sledziński, Z; Antosiewicz, J; Woźniak, M; Ostrowski, M M; Stanek, A; Wajda, Z

    1997-01-01

    This study aimed to investigate the protein peroxidation process in cerulein induced acute pancreatitis. Eighteen rats were divided into three equal groups: group 1 acted as control rats had intraperitoneal injection of 0.9% NaCl, in group 2 and 3 rats had injection of cerulein 40 micrograms kg-1 for 3 or 6h of induction period respectively. Protein carbonyls which reflect peroxidative damage were found to be increased after 3h up to 2.53 +/- 0.49 comparing to 1.05 +/- 0.17 in control group and returned to control level 0.95 +/- 0.04 after 6h. These data suggest that during acute pancreatitis free radicals may play an essential role in protein damage. Decrease in protein carbonyls content after 6h suggests an elevated proteolysis of oxidatively damaged proteins.

  16. Susceptibility and resistance to insecticides of Chagas disease vectors.

    Science.gov (United States)

    Zerba, E N

    1999-01-01

    Chemical control of Chagas disease vectors appears to be the best practical way to reduce the incidence of the disease. DDT was initially tested in the 1950s for the campaigns of control of Chagas disease vectors. Its low level of effectiveness against triatomine caused the failure of these control actions. HCH was then introduced in the southern cone and Dieldrin in the north of Latinoamerica. Starting in the late 1960s anticholinesterasic organophosphorus and carbamate compounds were introduced in the control of Chagas vectors. The use of pyrethroid compounds began in 1980. This family of insecticides is now the most important tool in triatomines control because of its favorable toxicological properties. Other types of insecticides also studied for Chagas vector control were the insect growth regulators and the antifeeding compounds. Because of the mode of action of these insecticides they are now considered just a potential complement of neurotoxic insecticides for integrated programmes of Triatomines control. Innovative formulations such as fumigant canister and insecticidal paints have been successfully developed in Latinoamerica with the World Health Organization support. Resistance to insecticides of triatomines is not yet a great problem in Chagas vectors. However, some resistant strains to pyrethroids have been found in Rhodnius prolixus from Venezuela and in Triatoma infestans from Brazil. Some cases of T. infestans incipient resistance to deltamethrin have been detected in Argentina. According to the control tools now available it is possible to expect the interruption of vector transmission of Chagas disease in the near future.

  17. Therapeutical approaches under investigation for treatment of Chagas disease.

    Science.gov (United States)

    Bahia, Maria Terezinha; Diniz, Lívia de Figueiredo; Mosqueira, Vanessa Carla Furtado

    2014-09-01

    A century after its discovery, American trypanosomiasis or Chagas disease remains a serious health problem in Latin America, where it affects around 7 - 8 million people. The prevalence of Chagas disease in the poorer parts of the world has meant that it has largely been neglected with limited progress that made in identifying new drugs for the treatment. The nitroheterocyclic drugs nifurtimox and benznidazole are first-line drugs available for Chagas disease with limitations that include variable efficacy, long treatment courses and toxicity. This review focuses on different therapeutic strategies that have been used for the discovery of new treatments for Chagas disease. These include combination chemotherapy, drug repositioning, re-dosing regimens for current drugs and the identification of new drugs with specified target profiles. There are currently several reasons for a more optimistic view about chemotherapy with Chagas disease. However, despite some progress being made in preclinical studies, there is yet to be an ideal drug or formulation for human treatment. One major drawback in the evaluation of potential Chagas disease therapeutics is the lack of tools available to perform the said evaluation. Indeed, there is a great need to discover a better biomarker that could determine the efficacy of potential chemotherapeutics in treated patients.

  18. [Protective effect of astragaloside IV against acute liver failure in experimental mice].

    Science.gov (United States)

    Liu, L; Li, S J; Zhou, Y

    2016-10-20

    Objective: To investigate the clinical effect of astragaloside IV in the early treatment of mice with acute liver failure and possible mechanisms. Methods: A mouse model of acute liver failure induced by D-galactosamine/lipopolysaccharide (D-GalN/LPS) was established, and the mice were given astragaloside IV at different doses. The survival rate of mice, alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels, liver histopathological changes, apoptosis of hepatocytes, and the expression of superoxide dismutase (SOD) and malondialdehyde (MDA) were measured in each group. The least significant difference test was used for data with homogeneity of variances, the Dunnett's T3 test was used for data with heterogeneity of variance, and the Kaplan-Meier method was used for survival analysis. Results: Compared with the model group, the high-dose astragaloside IV group had a significant increase in the 48-hour survival rate [60% (9/15) vs 13.3% (2/15), P liver histopathological indices and the degree of apoptosis of hepatocytes (P liver homogenate (P acute liver injury in mice, and its mechanisms may be associated with its effects against cell apoptosis and oxidative damage.

  19. Antinociceptive activity of acute and chronic administration of Murraya koenigii L. leaves in experimental animal models.

    Science.gov (United States)

    Patil, Rupali Arun; Langade, Padmaja Mukund; Dighade, Pramod Babarao; Hiray, Yogesh Ashok

    2012-01-01

    To evaluate the antinociceptive activity of acute and chronic administration of petroleum ether extract of Murraya koenigii L. leaves (PMK) and total alkaloids separated from petroleum ether extract of Murraya koenigii leaves (AMK) in mice. PMK was subjected for isolation of total alkaloid fraction AMK. The antinociceptive activity of PMK (100 and 300 mg/kg, p.o.) and AMK (100 and 300 mg/kg, p.o.), after acute and chronic administration (for 15 days), was evaluated using peripheral model like acetic acid-induced writhing method and central model like hot plate method and tail immersion method. Statistical analysis was carried out by one-way ANOVA followed by Dunnett's test. In acute studies, PMK and AMK significantly and dose-dependently reduced the number of acetic acid-induced writhing, significantly increased the latency of paw licking in hot plate method, and significantly increased the basal reaction time in tail immersion method. With chronic administration of PMK and AMK, highest activity was observed on day 9 in acetic acid-induced writhing model. In hot plate and tail immersion method, chronic administration of PMK and AMK initially showed fluctuating responses but produced highest degree of antinociception on day 9 of the study. The degree of antinociception produced by PMK and AMK at the end of 15 days study suggest that Murraya koenigii has potential to use as an analgesic.

  20. Effects of urtica dioica extract on experimental acute pancreatitis model in rats.

    Science.gov (United States)

    Yilmaz, Baris; Basar, Omer; Aktas, Bora; Altinbas, Akif; Ekiz, Fuat; Büyükcam, Fatih; Albayrak, Aynur; Ginis, Zeynep; Oztürk, Gülfer; Coban, Sahin; Ucar, Engin; Kaya, Oskay; Yüksel, Osman; Caner, Sedat; Delibasi, Tuncay

    2014-01-01

    Acute pancreatitis is the acute inflammation of pancreas and peripancreatic tissues, and distant organs are also affected. The aim of this study was to investigate the effect of Urtica dioica extract (UDE) treatment on cerulein induced acute pancreatitis in rats. Twenty-one Wistar Albino rats were divided into three groups: Control, Pancreatitis, and UDE treatment group. In the control group no procedures were performed. In the pancreatitis and treatment groups, pancreatitis was induced with intraperitoneal injection of cerulein, followed by intraperitoneal injection of 1 ml saline (pancreatitis group) and 1 ml 5.2% UDE (treatment group). Pancreatic tissues were examined histopathologically. Pro-inflammatory cytokines (tumor necrosis factor-α), amylase and markers of apoptosis (M30, M65) were also measured in blood samples. Immunohistochemical staining was performed with Caspase-3 antibody. Histopathological findings in the UDE treatment group were less severe than in the pancreatitis group (5.7 vs 11.7, p = 0.010). TNF-α levels were not statistically different between treated and control groups (63.3 vs. 57.2, p = 0.141). UDE treatment was associated with less apoptosis [determined by M30, caspase-3 index (%)], (1.769 vs. 0.288, p = 0.056; 3% vs. 2.2%, p = 0.224; respectively). UDE treatment of pancreatitis merits further study.

  1. Ascitic fluid of experimental severe acute pancreatitis modulates the function of peritoneal macrophages.

    Science.gov (United States)

    Satoh, A; Shimosegawa, T; Masamune, A; Fujita, M; Koizumi, M; Toyota, T

    1999-10-01

    Although the pathophysiology of acute pancreatitis appears to be greatly influenced by the production of ascites, little is known about the mechanism. To investigate the effects of pancreatitis-associated ascitic fluid (PAAF) on macrophage function, we examined the effects of PAAF obtained from a rat model of severe acute pancreatitis on the ability of peritoneal macrophages to produce tumor necrosis factor-alpha (TNF-alpha). In addition, we compared the responses of PAAF-treated and PAAF-untreated macrophages to lipopolysaccharide (LPS) by evaluating their TNF-alpha production and nuclear factor-kappaB (NFkappaB) activation. Incubation of peritoneal macrophages with the PAAF led to the rapid and prolonged activation of NF-kappaB and to TNF-alpha production. Pyrrolidine dithiocarbamate, a potent inhibitor of NF-kappaB activation, attenuated the macrophage TNF-alpha production by PAAF. Macrophages produced TNF-alpha in response to LPS, but the cytokine production was significantly reduced when macrophages were pretreated with PAAF. The suppression of TNF-alpha production by PAAF pretreatment accompanied the impairment of NF-kappaB activation in response to LPS. These results indicate that the PAAF of severe acute pancreatitis may play important roles in the pathologic course of this disease through its effects on macrophage function.

  2. Integrate Study of a Bolivian Population Infected by Trypanosoma cruzi, the Agent of Chagas Disease

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    Brenière Simone Frédérique

    2002-01-01

    Full Text Available A cross section of a human population (501 individuals selected at random, and living in a Bolivian community, highly endemic for Chagas disease, was investigated combining together clinical, parasitological and molecular approaches. Conventional serology and polymerase chain reaction (PCR indicated an active transmission of the infection, a high seroprevalence (43.3% ranging from around 12% in 45 years, and a high sensitivity (83.8% and specificity of PCR. Abnormal ECG tracing was predominant in chagasic patients and was already present among individuals younger than 13 years. SAPA (shed acute phase antigen recombinant protein and the synthetic peptide R-13 were used as antigens in ELISA tests. The reactivity of SAPA was strongly associated to Trypanosoma cruzi infection and independent of the age of the patients but was not suitable neither for universal serodiagnosis nor for discrimination of specific phases of Chagas infection. Anti-R-13 response was observed in 27.5% only in chagasic patients. Moreover, anti-R13 reactivity was associated with early infection and not to cardiac pathology. This result questioned previous studies, which considered the anti-R-13 response as a marker of chronic Chagas heart disease. The major clonets 20 and 39 (belonging to Trypanosoma cruzi I and T. cruzi II respectively which circulate in equal proportions in vectors of the studied area, were identified in patients' blood by PCR. Clonet 39 was selected over clonet 20 in the circulation whatever the age of the patient. The only factor related to strain detected in patients' blood, was the anti-R-13 reactivity: 37% of the patients infected by clonet 39 (94 cases had anti-R13 antibodies contrasting with only 6% of the patients without clonet 39 (16 cases.

  3. Experimental acute rumen acidosis in sheep: consequences on clinical, rumen, and gastrointestinal permeability conditions and blood chemistry.

    Science.gov (United States)

    Minuti, A; Ahmed, S; Trevisi, E; Piccioli-Cappelli, F; Bertoni, G; Jahan, N; Bani, P

    2014-09-01

    Acute acidosis was induced in sheep, and gastrointestinal permeability was assessed by using lactulose as a permeability marker. Metabolism was evaluated by monitoring blood metabolites. Four rams (72.5 ± 4.6 kg BW) were used in a 2 × 2 changeover design experiment. The experimental period lasted 96 h from -24 to 72 h. After 24 h of fasting (from -24 to 0 h) for both controls and acidosis-induced rams (ACID), 0.5 kg of wheat flour was orally dosed at 0 and 12 h of the experimental period to ACID, while the basal diet (grass hay, ad libitum) was restored to control. At 24 h, a lactulose solution (30 g of lactulose in 200 mL of water) was orally administered. Blood samples were collected at -24, 0, 24, 48, and 72 h of the experimental periods for the analysis of metabolic profiles and during the 10 h after lactulose dosage to monitor lactulose changes in blood. In addition, rumen and fecal samples were collected at 24 h of the experimental period. The acidotic challenge markedly reduced (P rumen pH and VFA but increased rumen d- and l-lactic acid (P acidosis was effectively induced by our model. The increase of lactulose in blood in ACID indicates that gastrointestinal permeability for the marker increased and the large increment after 2 h from dosage suggests that most of the passage occurred through the rumen or abomasal walls.

  4. Movement does not promote recovery of motor output following acute experimental muscle pain

    DEFF Research Database (Denmark)

    Schabrun, Siobhan M.; Palsson, Thorvaldur Skuli; Thapa, Tribikram

    2018-01-01

    Objective.:  To examine the effect of motor activity on the magnitude and duration of altered corticomotor output following experimental muscle pain. Design. : Experimental, pre-post test. Setting. : University laboratory. Subjects. : Twenty healthy individuals. Methods.:  Participants were rando....... Understanding corticomotor depression in the postpain period and what factors promote recovery has relevance for clinical pain syndromes where ongoing motor dysfunction, in the absence of pain, may predispose to symptom persistence or recurrence....

  5. Experimental alveolitis in rats: microbiological, acute phase response and histometric characterization of delayed alveolar healing

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    Moacyr Tadeu Vicente Rodrigues

    2011-06-01

    Full Text Available The pathogenesis of alveolitis is not well known and therefore experimental situations that mimic some features of this disease should be developed. OBJECTIVE: In this study, the evolution of the experimentally induced infection in rat sockets is characterized, which leads to clinical signs of suppurative alveolitis with remarkable wound healing disturbs. MATERIAL AND METHODS: Non-infected (Group I and experimentally infected sockets in Rattus novergicus (Group II were histometrically evaluated regarding the kinetics of alveolar healing. In addition, the characterization of the present bacteria in inoculation material and the serum levels of C-reactive protein (CRP were performed. The detected species were Capnocytophaga ochracea, Fusobacterium nucleatum ss nucleatum, Prevotella melaninogenica, Streptococcus anginosus, Treponema socranskii and Streptococcus sanguis. RESULTS: All experimentally infected rats developed suppurative alveolitis, showing higher levels of CRP in comparison to those non-infected ones. Furthermore, infected rats presented a significant delayed wound healing as measured by the histometric analysis (higher persistent polymorphonuclear infiltrate and lower density of newly formed bone. CONCLUSION: These findings indicate that rat sockets with experimentally induced infection produced higher levels of serum CRP, showing the potential of disseminated infection and a disturb in the alveolar repair process in an interesting experimental model for alveolitis studies.

  6. Fase crônica cardíaca fibrosante da Tripanossomíase cruzi experimental no cão

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    Marta de Lana

    1988-09-01

    Full Text Available Os autores documentam a cardiopatia difusa fibrosante, com todos os sintomas clínicos e dados de autópsia pertinentes à insuficiência cardíaca congestiva, em um dos 21 cães infectados com a cepa Colombiana (cinco morreram na fase aguda e quatro continuam vivos e cinco, dos 13 infectados com a cepa Berenice-78 (oito morreram na fase aguda, num período de oito anos de observação. Em vista destes resultados, os autores sugerem que o cão possa vir a ser um modelo experimental, adequado para o estudo da história natural da doença de Chagas, preenchendo os requisitos estabelecidos pelo Comitê Assessor de Doença de Chagas do Programa Especial de Pesquisa e Treinamento em Doenças Tropicais da Organização Mundial de Saúde.The authors found the fibrosing chronic chagasic cardiopathy with congestive heartfailure in one out of the 21 dogs infected with the Colombian strain (five died in acutephase andfour are alivefive out of the 13 animais infected with the Berenice-78 strain eight died in acute phase were observed until eight years of infection with T. cruzi. In view of these results, the author suggest that the dog could be a suitable experimental model for the study of the natural history of Chagas' disease. The dog conforms with the requisites of the World Health Organization (WHO Steering Committee of Chagas' disease of the Programmefor Research Training in Tropical Diseases.

  7. Effects of acute memantine administration on MATRICS Consensus Cognitive Battery performance in psychosis: Testing an experimental medicine strategy.

    Science.gov (United States)

    Bhakta, Savita G; Chou, Hsun-Hua; Rana, Brinda; Talledo, Jo A; Balvaneda, Bryan; Gaddis, Laura; Light, Gregory A; Swerdlow, Neal R

    2016-06-01

    Pro-cognitive agents for chronic psychotic disorders (CPDs) might be detected via experimental medicine models, in which neural targets engaged by the drug predict sensitivity to the drug's pro-cognitive effects. This study aims to use an experimental medicine model to test the hypothesis that "target engagement" predicts pro-cognitive effects of the NMDA antagonist, memantine (MEM), in CPDs. MATRICS Consensus Cognitive Battery (MCCB) performance was assessed in CPD (n = 41) and healthy subjects (HS; n = 41) in a double-blind, randomized cross-over design of acute (single dose) MEM (placebo vs. 10 or 20 mg p.o.). Measures of prepulse inhibition (PPI) and mismatch negativity previously reported from this cohort substantiated target engagement. Biomarkers predicting MEM neurocognitive sensitivity were assessed. Testing confirmed MCCB deficits associated with CPD diagnosis, age, and anticholinergic exposure. MEM (20 mg p.o.) reduced MCCB performance in HS. To control for significant test order effects, an "order-corrected MEM effect" (OCME) was calculated. In CPD subjects, greater age, positive MEM effects on PPI, and SNP rs1337697 (within the ionotropic NMDA receptor gene, GRIN3A) predicted greater positive OCME with 20 mg MEM. An experimental medicine model to assess acute pro-cognitive drug effects in CPD subjects is feasible but not without challenges. A single MEM 20 mg dose had a negative impact on neurocognition among HS. In CPD patients, age, MEM effects on PPI, and rs1337697 predicted sensitivity to the neurocognitive effects of MEM. Any potential clinical utility of these predictive markers for pro-cognitive effects of MEM in subgroups of CPD patients cannot be inferred without a validating clinical trial.

  8. Molecular Epidemiology of Human Oral Chagas Disease Outbreaks in Colombia

    Science.gov (United States)

    Ramírez, Juan David; Montilla, Marleny; Cucunubá, Zulma M.; Floréz, Astrid Carolina; Zambrano, Pilar; Guhl, Felipe

    2013-01-01

    Background Trypanosoma cruzi, the causative agent of Chagas disease, displays significant genetic variability revealed by six Discrete Typing Units (TcI-TcVI). In this pathology, oral transmission represents an emerging epidemiological scenario where different outbreaks associated to food/beverages consumption have been reported in Argentina, Bolivia, Brazil, Ecuador and Venezuela. In Colombia, six human oral outbreaks have been reported corroborating the importance of this transmission route. Molecular epidemiology of oral outbreaks is barely known observing the incrimination of TcI, TcII, TcIV and TcV genotypes. Methodology and Principal Findings High-throughput molecular characterization was conducted performing MLMT (Multilocus Microsatellite Typing) and mtMLST (mitochondrial Multilocus Sequence Typing) strategies on 50 clones from ten isolates. Results allowed observing the occurrence of TcI, TcIV and mixed infection of distinct TcI genotypes. Thus, a majority of specific mitochondrial haplotypes and allelic multilocus genotypes associated to the sylvatic cycle of transmission were detected in the dataset with the foreseen presence of mitochondrial haplotypes and allelic multilocus genotypes associated to the domestic cycle of transmission. Conclusions These findings suggest the incrimination of sylvatic genotypes in the oral outbreaks occurred in Colombia. We observed patterns of super-infection and/or co-infection with a tailored association with the severe forms of myocarditis in the acute phase of the disease. The transmission dynamics of this infection route based on molecular epidemiology evidence was unraveled and the clinical and biological implications are discussed. PMID:23437405

  9. Molecular epidemiology of human oral Chagas disease outbreaks in Colombia.

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    Juan David Ramírez

    Full Text Available BACKGROUND: Trypanosoma cruzi, the causative agent of Chagas disease, displays significant genetic variability revealed by six Discrete Typing Units (TcI-TcVI. In this pathology, oral transmission represents an emerging epidemiological scenario where different outbreaks associated to food/beverages consumption have been reported in Argentina, Bolivia, Brazil, Ecuador and Venezuela. In Colombia, six human oral outbreaks have been reported corroborating the importance of this transmission route. Molecular epidemiology of oral outbreaks is barely known observing the incrimination of TcI, TcII, TcIV and TcV genotypes. METHODOLOGY AND PRINCIPAL FINDINGS: High-throughput molecular characterization was conducted performing MLMT (Multilocus Microsatellite Typing and mtMLST (mitochondrial Multilocus Sequence Typing strategies on 50 clones from ten isolates. Results allowed observing the occurrence of TcI, TcIV and mixed infection of distinct TcI genotypes. Thus, a majority of specific mitochondrial haplotypes and allelic multilocus genotypes associated to the sylvatic cycle of transmission were detected in the dataset with the foreseen presence of mitochondrial haplotypes and allelic multilocus genotypes associated to the domestic cycle of transmission. CONCLUSIONS: These findings suggest the incrimination of sylvatic genotypes in the oral outbreaks occurred in Colombia. We observed patterns of super-infection and/or co-infection with a tailored association with the severe forms of myocarditis in the acute phase of the disease. The transmission dynamics of this infection route based on molecular epidemiology evidence was unraveled and the clinical and biological implications are discussed.

  10. Mechanisms of acute kidney injury induced by experimental Lonomia obliqua envenomation.

    Science.gov (United States)

    Berger, Markus; Santi, Lucélia; Beys-da-Silva, Walter O; Oliveira, Fabrício Marcus Silva; Caliari, Marcelo Vidigal; Yates, John R; Vieira, Maria Aparecida Ribeiro; Guimarães, Jorge Almeida

    2015-03-01

    Lonomia obliqua caterpillar envenomation causes acute kidney injury (AKI), which can be responsible for its deadly actions. This study evaluates the possible mechanisms involved in the pathogenesis of renal dysfunction. To characterize L. obliqua venom effects, we subcutaneously injected rats and examined renal functional, morphological and biochemical parameters at several time points. We also performed discovery-based proteomic analysis to measure protein expression to identify molecular pathways of renal disease. L. obliqua envenomation causes acute tubular necrosis, which is associated with renal inflammation; formation of hematic casts, resulting from intravascular hemolysis; increase in vascular permeability and fibrosis. The dilation of Bowman's space and glomerular tuft is related to fluid leakage and intra-glomerular fibrin deposition, respectively, since tissue factor procoagulant activity increases in the kidney. Systemic hypotension also contributes to these alterations and to the sudden loss of basic renal functions, including filtration and excretion capacities, urinary concentration and maintenance of fluid homeostasis. In addition, envenomed kidneys increase the expression of proteins involved in cell stress, inflammation, tissue injury, heme-induced oxidative stress, coagulation and complement system activation. Finally, the localization of the venom in renal tissue agrees with morphological and functional alterations, suggesting also a direct nephrotoxic activity. In conclusion, the mechanisms of L. obliqua-induced AKI are complex involving mainly glomerular and tubular functional impairment and vascular alterations. These results are important to understand the mechanisms of renal injury and may suggest more efficient ways to prevent or attenuate the pathology of Lonomia's envenomation.

  11. Renoprotective Effects of AVE0991, a Nonpeptide Mas Receptor Agonist, in Experimental Acute Renal Injury

    Science.gov (United States)

    Barroso, Lívia Corrêa; Silveira, Kátia Daniela; Lima, Cristiano Xavier; Borges, Valdinéria; Bader, Michael; Rachid, Milene; Santos, Robson Augusto Souza; Souza, Danielle Gloria; Simões e Silva, Ana Cristina; Teixeira, Mauro Martins

    2012-01-01

    Renal ischemia and reperfusion (I/R) is the major cause of acute kidney injury in hospitalized patients. Mechanisms underlying reperfusion-associated injury include recruitment and activation of leukocytes and release of inflammatory mediators. In this study, we investigated the renal effects of acute administration of AVE0991, an agonist of Mas, the angiotensin-(1–7) receptor, the angiotensin-(1–7) receptor, in a murine model of renal I/R. Male C57BL/6 wild-type or Mas−/− mice were subjected to 30 min of bilateral ischemia and 24 h of reperfusion. Administration of AVE0991 promoted renoprotective effects, as seen by improvement of function, decreased tissue injury, prevention of local and remote leucocyte infiltration, and release of the chemokine, CXCL1. I/R injury was similar in WT and Mas−/− mice, suggesting that endogenous activation of this receptor does not control renal damage under baseline conditions. In conclusion, pharmacological interventions using Mas receptor agonists may represent a therapeutic opportunity for the treatment of renal I/R injury. PMID:22319645

  12. Renoprotective Effects of AVE0991, a Nonpeptide Mas Receptor Agonist, in Experimental Acute Renal Injury

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    Lívia Corrêa Barroso

    2012-01-01

    Full Text Available Renal ischemia and reperfusion (I/R is the major cause of acute kidney injury in hospitalized patients. Mechanisms underlying reperfusion-associated injury include recruitment and activation of leukocytes and release of inflammatory mediators. In this study, we investigated the renal effects of acute administration of AVE0991, an agonist of Mas, the angiotensin-(1–7 receptor, the angiotensin-(1–7 receptor, in a murine model of renal I/R. Male C57BL/6 wild-type or Mas−/− mice were subjected to 30 min of bilateral ischemia and 24 h of reperfusion. Administration of AVE0991 promoted renoprotective effects, as seen by improvement of function, decreased tissue injury, prevention of local and remote leucocyte infiltration, and release of the chemokine, CXCL1. I/R injury was similar in WT and Mas−/− mice, suggesting that endogenous activation of this receptor does not control renal damage under baseline conditions. In conclusion, pharmacological interventions using Mas receptor agonists may represent a therapeutic opportunity for the treatment of renal I/R injury.

  13. Mechanisms of Acute Kidney Injury Induced by Experimental Lonomia obliqua Envenomation

    Science.gov (United States)

    Berger, Markus; Santi, Lucélia; Beys-da-Silva, Walter O.; Oliveira, Fabrício Marcus Silva; Caliari, Marcelo Vidigal; Yates, John R.; Ribeiro, Maria Aparecida; Guimarães, Jorge Almeida

    2015-01-01

    Background Lonomia obliqua caterpillar envenomation causes acute kidney injury (AKI), which can be responsible for its deadly actions. This study evaluates the possible mechanisms involved in the pathogenesis of renal dysfunction. Methods To characterize L. obliqua venom effects we subcutaneously injected rats and examined renal functional, morphological and biochemical parameters at several time points. We also performed discovery based proteomic analysis to measure protein expression to identify molecular pathways of renal disease. Results L. obliqua envenomation causes acute tubular necrosis, which is associated with renal inflammation; formation of hematic casts, resulting from intravascular hemolysis; increase in vascular permeability and fibrosis. The dilation of Bowman’s space and glomerular tuft is related to fluid leakage and intra-glomerular fibrin deposition, respectively, since tissue factor procoagulant activity increases in the kidney. Systemic hypotension also contributes to these alterations and to the sudden loss of basic renal functions, including filtration and excretion capacities, urinary concentration and maintenance of fluid homeostasis. In addition, envenomed kidneys increases expression of proteins involved in cell stress, inflammation, tissue injury, heme-induced oxidative stress, coagulation and complement system activation. Finally, the localization of the venom in renal tissue agrees with morphological and functional alterations, suggesting also a direct nephrotoxic activity. Conclusions Mechanisms of L. obliqua-induced AKI are complex involving mainly glomerular and tubular functional impairment and vascular alterations. These results are important to understand the mechanisms of renal injury and may suggest more efficient ways to prevent or attenuate the pathology of Lonomia’s envenomation. PMID:24798088

  14. Cardiac Function Remains Impaired Despite Reversible Cardiac Remodeling after Acute Experimental Viral Myocarditis

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    Peter Moritz Becher

    2017-01-01

    Full Text Available Background. Infection with Coxsackievirus B3 induces myocarditis. We aimed to compare the acute and chronic phases of viral myocarditis to identify the immediate effects of cardiac inflammation as well as the long-term effects after resolved inflammation on cardiac fibrosis and consequently on cardiac function. Material and Methods. We infected C57BL/6J mice with Coxsackievirus B3 and determined the hemodynamic function 7 as well as 28 days after infection. Subsequently, we analyzed viral burden and viral replication in the cardiac tissue as well as the expression of cytokines and matrix proteins. Furthermore, cardiac fibroblasts were infected with virus to investigate if viral infection alone induces profibrotic signaling. Results. Severe cardiac inflammation was determined and cardiac fibrosis was consistently colocalized with inflammation during the acute phase of myocarditis. Declined cardiac inflammation but no significantly improved hemodynamic function was observed 28 days after infection. Interestingly, cardiac fibrosis declined to basal levels as well. Both cardiac inflammation and fibrosis were reversible, whereas the hemodynamic function remains impaired after healed viral myocarditis in C57BL/6J mice.

  15. Sexual transmission of American trypanosomiasis in humans: a new potential pandemic route for Chagas parasites

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    Perla F Araujo

    Full Text Available BACKGROUND The Trypanosoma cruzi infection endemic in Latin America has now spread to several countries across four continents; this endemic involves triatomine vector-free protists. We hypothesised that the sexual transmission of T. cruzi contributes to the ongoing spread of Chagas disease. OBJECTIVES A short-term longitudinal study was conducted to evaluate this hypothesis. METHODS The study population comprised 109 subjects from four families, among whom 21 had been diagnosed with acute Chagas disease by direct parasitological analysis. Blood mononuclear cells and serum samples were obtained from each study subject once per year for three consecutive years. Enzyme-linked immunosorbent assay (ELISA and indirect immunofluorescence serological examinations were used to detect specific T. cruzi antibodies. Polymerase chain reaction of T. cruzi DNA revealed 188-nucleotide bands, which hybridised to a specific radiolabelled probe and were confirmed by cloning and sequencing. RESULTS Three independent assessments at different time points revealed T. cruzi nuclear DNA footprints in 76% (83/109 of the study population with active infection. In contrast, the ELISA and indirect immunofluorescence assays detected the T. cruzi antibody in 28.4% (31/109 of the study samples. Moreover, the semen from 82.6% (19/23 of subjects people revealed harboured the 188- bp base pair T. cruzi footprint. Interestingly, the ejaculates of nuclear DNA-positive Chagas patient transmitted the T. cruzi upon peritoneal injection or infusion in the vagina of mice, and amastigotes were detected in the skeletal muscle, myocardium, vas deferens, and uterine tube. MAIN CONCLUSIONS T. cruzi infections can be transmitted from females or males to naïve mates through intercourse, and progeny showed discrepancies between the ratios of nuclear DNA footprints and specific antibody that can be explained by the tolerance attained during early embryo growth. Additional studies are needed to

  16. Geographic Distribution of Chagas Disease Vectors in Brazil Based on Ecological Niche Modeling

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    Rodrigo Gurgel-Gonçalves

    2012-01-01

    Full Text Available Although Brazil was declared free from Chagas disease transmission by the domestic vector Triatoma infestans, human acute cases are still being registered based on transmission by native triatomine species. For a better understanding of transmission risk, the geographic distribution of Brazilian triatomines was analyzed. Sixteen out of 62 Brazilian species that both occur in >20 municipalities and present synanthropic tendencies were modeled based on their ecological niches. Panstrongylus geniculatus and P. megistus showed broad ecological ranges, but most of the species sort out by the biome in which they are distributed: Rhodnius pictipes and R. robustus in the Amazon; R. neglectus, Triatoma sordida, and T. costalimai in the Cerrado; R. nasutus, P. lutzi, T. brasiliensis, T. pseudomaculata, T. melanocephala, and T. petrocchiae in the Caatinga; T. rubrovaria in the southern pampas; T. tibiamaculata and T. vitticeps in the Atlantic Forest. Although most occurrences were recorded in open areas (Cerrado and Caatinga, our results show that all environmental conditions in the country are favorable to one or more of the species analyzed, such that almost nowhere is Chagas transmission risk negligible.

  17. Molecular diagnostics for Chagas disease: up to date and novel methodologies.

    Science.gov (United States)

    Alonso-Padilla, Julio; Gallego, Montserrat; Schijman, Alejandro G; Gascon, Joaquim

    2017-07-01

    Chagas disease is caused by the parasite Trypanosoma cruzi. It affects 7 million people, mainly in Latin America. Diagnosis is usually made serologically, but at some clinical scenarios serology cannot be used. Then, molecular detection is required for early detection of congenital transmission, treatment response follow up, and diagnosis of immune-suppression reactivation. However, present tests are technically demanding and require well-equipped laboratories which make them unfeasible in low-resources endemic regions. Areas covered: Available molecular tools for detection of T. cruzi DNA, paying particular attention to quantitative PCR protocols, and to the latest developments of user-friendly molecular diagnostic methodologies. Expert commentary: In the absence of appropriate biomarkers, molecular diagnosis is the only option for the assessment of treatment response. Besides, it is very useful for the early detection of acute infections, like congenital cases. Since current Chagas disease molecular tests are restricted to referential labs, research efforts must focus in the implementation of easy-to-use diagnostic tools in order to overcome the access to diagnosis gap.

  18. A contribution to the study of acute schistosomiasis (an experimental trial Contribuição ao estudo da esquistossomose aguda (uma tentativa experimental

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    Zilton A. Andrade

    1987-09-01

    Full Text Available In an attempt to establish an experimental model of acute schistosomiasis, sequential histological changes were investigated in the skin, lung, liver and spleen of mice infected with 30 or 100 cercariae of Schistosoma mansoni according to four sets of experiments: single infection, repeated infections, unisexual infection and infection in mice born from infected mothers. Animals were killed every other day from exposure up to 50 days after infection. Only mild, isolated, focal inflammatory changes were found before the appearance of mature eggs in the liver, even when repeated infections were made. Severe changes of reactive hepatitis and splenitis appeared suddenly when the first mature eggs were deposited, around the 37th to 42nd day after infection. The mature eggs induced lytic and coagulative necrosis of hepatocytes around them which was soon followed by dense infiltration of eosinophils. So, mature egg-induced lesions appeared as the major factors in the pathogenesis of acute schistosomiasis in mice. Mice born from infected mothers were apparently able to rapidly modulate the egg-lesions, forming early fibrotic granulomas. The murine model of acute schistosomiasis appeared adequate for the study of pathology and pathogenesis of acute schistosomiasis.Numa tentativa para se estabelecer um modelo experimental para o estudo da esquistossomose aguda foram estudadas as alterações presentes na pele, pulmões, fígado e baço de comundongos submetidos a infecção com 30 ou 100 cercarias do Schistosoma mansoni e divididos em quatro tipos de experimentos: infecção simples, infecções repetidas, infecção unissexuada e infecção em animais provenientes de mães infectadas. Os animais foram sacrificados em dias alternados a partir do momento da infecção até 50 dias depois. As lesões encontadas na fase pré-postural foram discretas e poucas, mesmo quando os animais foram submetidos a infecções repetidas. As alterações mais súbitas e

  19. Effects of astaxanthin in mice acutely infected with Trypanosoma cruzi

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    Contreras-Ortiz José María Eloy

    2017-01-01

    Full Text Available During Trypanosoma cruzi infection, oxidative stress is considered a contributing factor for dilated cardiomyopathy development. In this study, the effects of astaxanthin (ASTX were evaluated as an alternative drug treatment for Chagas disease in a mouse model during the acute infection phase, given its anti-inflammatory, immunomodulating, and anti-oxidative properties. ASTX was tested in vitro in parasites grown axenically and in co-culture with Vero cells. In vivo tests were performed in BALB/c mice (4–6 weeks old infected with Trypanosoma cruzi and supplemented with ASTX (10 mg/kg/day and/or nifurtimox (NFMX; 100 mg/kg/day. Results show that ASTX has some detrimental effects on axenically cultured parasites, but not when cultured with mammalian cell monolayers. In vivo, ASTX did not have any therapeutic value against acute Trypanosoma cruzi infection, used either alone or in combination with NFMX. Infected animals treated with NFMX or ASTX/NFMX survived the experimental period (60 days, while infected animals treated only with ASTX died before day 30 post-infection. ASTX did not show any effect on the control of parasitemia; however, it was associated with an increment in focal heart lymphoplasmacytic infiltration, a reduced number of amastigote nests in cardiac tissue, and less hyperplasic spleen follicles when compared to control groups. Unexpectedly, ASTX showed a negative effect in infected animals co-treated with NFMX. An increment in parasitemia duration was observed, possibly due to ASTX blocking of free radicals, an anti-parasitic mechanism of NFMX. In conclusion, astaxanthin is not recommended during the acute phase of Chagas disease, either alone or in combination with nifurtimox.

  20. First report of a family outbreak of Chagas disease in French Guiana and posttreatment follow-up.

    Science.gov (United States)

    Blanchet, Denis; Brenière, Simone Frédérique; Schijman, Alejandro G; Bisio, Margarita; Simon, Stéphane; Véron, Vincent; Mayence, Claire; Demar-Pierre, Magalie; Djossou, Félix; Aznar, Christine

    2014-12-01

    The outbreak of acute Chagas disease due to oral transmission of the parasite is a well-known phenomenon mainly occurring in the Amazon. Such an event is described here for the first time in French Guiana. Eight patients of the same family, presenting epidemiological and clinical histories compatible with recent Trypanosoma cruzi infection of Chagas disease due to the ingestion of palm Oenocarpus bacaba juice were, rather late after the putative date of infection, underwent four parasitological and two serological specific tests for confirmation of the diagnosis. Real-time PCR results were positive for all the patients; strains were isolated by hemoculture from four patients, PCR identification of TcI DTU was made for six patients, while parasites were not detected in any of the patients by direct microscopic examination. The results of two serologic tests were positive. All patients were treated with benznidazole, and two patients were additionally given nifurtimox. A 6-year follow-up was possible for six patients. Real-time PCR was negative for these patients after 1 year, while the antibody rates decreased slowly and serology results were negative only after several years (1-5 years). Our findings confirm the occurrence of an outbreak of Chagas infection in members of the same family, with the oral mode of infection being the most likely hypothesis to explain this group of cases. Our results show the successful treatment of patients infected by TcI and the usefulness of real-time PCR for the emergency diagnosis of recent Chagas disease cases and in posttreatment follow-up. Copyright © 2014 Elsevier B.V. All rights reserved.

  1. Cardiomiopatía de Chagas.

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    Fernando Rosas A.

    2000-08-01

    Full Text Available

    La cardiomiopatía de Chagas es la causa más frecuente de cardiomiopatía en América Latina. Se constituye en la cuarta enfermedad parasitaria del continente, y es uno de los mayores problemas de salud pública en Colombia estimándose que existen 1.200.000 personas infectadas y que de éstos proba-blemente 25% desarrollaran una miocardiopatia crónica.

    En nuestro país pocas series clínicas han sido descritas, generalmente asociadas a falla cardíaca secundaria a una cardiomiopatía dilatada. El propósito de este trabajo es presentar una reseña histórica de la enfermedad en la que se incluyen los primeros trabajos clínicos desarrollados en nuestro medio. Así mismo, algunos aspectos de la fisiopatología y de la evolución clínica. Finalmente presentaremos la reciente experiencia acumulada en nuestro país en este campo por diferentes investigadores.

    Reseña Histórica
    En el año 1909 fue publicado el artículo original del Dr. Carlos Chagas, titulado “Nueva Trypanosomiasis Humana: estudios sobre la morfología y el ciclo evolutivo del Schizotrypanum Cruzi, agente etiológico de una nueva entidad mórbida en el hombre” (1. En él se describe como el Dr. Chagas, fue encomendado en 1907, por el Dr. Oswaldo Cruz (Director del instituto que posteriormente llevó su nombre, para ejecutar una campaña antipalúdica en los servicios de construcción de ferrocarriles en el norte del estado de Minas Gerais.

    En esa zona conoció la existencia de una hematófago denominado por los campesinos como “Barbeiro”, llamado así por que su picadura se localizaba usualmente en el rostro y era poco sintomática. El insecto habitaba en domicilios humanos, atacaba al hombre en la noche (después de apagar las luces, se ocultaba durante el día en las paredes y en los techos de las casas construidas en bahareque y paja. El hematófago fue identificado como perteneciente a la familia Reduviidae. Algunos de los

  2. Noninvasive In Vivo Quantification of Neutrophil Elastase Activity in Acute Experimental Mouse Lung Injury

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    Sylvie Kossodo

    2011-01-01

    Full Text Available We developed a neutrophil elastase-specific near-infrared fluorescence imaging agent, which, combined with fluorescence molecular tomographic imaging, allowed us to detect and quantify neutrophil elastase activity in vivo, in real time, and noninvasively in an acute model of lung injury (ALI. Significantly higher fluorescent signal was quantified in mice with LPS/fMLP-induced ALI as compared to healthy controls, correlating with increases in the number of bronchoalveolar lavage cells, neutrophils, and elastase activity. The agent was significantly activated ex vivo in lung sections from ALI but not from control mice, and this activation was ablated by the specific inhibitor sivelestat. Treatment with the specific inhibitor sivelestat significantly reduced lung signal in mice with ALI. These results underscore the unique ability of fluorescence molecular imaging to quantify specific molecular processes in vivo, crucial for understanding the mechanisms underlying disease progression and for assessing and monitoring novel pharmacological interventions.

  3. STUDIES ON ACUTE DISSEMINATED ENCEPHALOMYELITIS PRODUCED EXPERIMENTALLY IN RHESUS MONKEYS. III

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    Kabat, Elvin A.; Wolf, Abner; Bezer, Ada E.

    1948-01-01

    The factor in brain tissue which induces acute disseminated encephalomyelitis, when injected into rhesus monkeys as an emulsion with adjuvants, has been found in human, monkey, rabbit, and chicken brain but is absent from frog and fish brain. It is unaffected by fixation of the brain in formalin, by boiling, and by treatment with ultrasound. It is present in the spinal cord of 3 day old rabbits but does not appear in the rabbit cerebrum until about the 12th day of life; in this respect it parallels the laying down of myelin. Attempts to produce the encephalomyelitis passively with large quantities of serum or of cell exudates, and suspensions of cells from spleen and lymph node from monkeys with encephalomyelitis, were unsuccessful. PMID:18884901

  4. Preventive effect of the microalga Chlamydomonas debaryana on the acute phase of experimental colitis in rats.

    Science.gov (United States)

    Avila-Román, Javier; Talero, Elena; Alcaide, Antonio; Reyes, Carolina de Los; Zubía, Eva; García-Mauriño, Sofía; Motilva, Virginia

    2014-10-14

    Inflammatory bowel diseases (IBD) are characterised by chronic uncontrolled inflammation of intestinal mucosa. Diet and nutritional factors have emerged as possible interventions for IBD. Microalgae are rich sources of n-3 PUFA and derived oxylipins. Oxylipins are lipid mediators involved in the resolution of many inflammatory disorders. The aim of the present study was to investigate the effects of the oxylipin-containing biomass of the microalga Chlamydomonas debaryana and its major oxylipin constituent, (9Z,11E,13S,15Z)-13-hydroxyoctadeca-9,11,15-trienoic acid ((13S)-HOTE), on acute 2,4,6-trinitrobenzenesulfonic acid (TNBS)-induced colitis in rats. Lyophilised microalgal biomass and (13S)-HOTE were administered by oral route 48, 24 and 1 h before the induction of colitis and 24 h later, and the rats were killed after 48 h. The treatment with the lyophilised microalga and (13S)-HOTE improved body-weight loss and colon shortening, as well as attenuated the extent of colonic damage and increased mucus production. Cellular neutrophil infiltration, with the subsequent increase in myeloperoxidase levels induced by TNBS, were also reduced after the administration of the lyophilised microalga or (13S)-HOTE. The anti-inflammatory effects of these treatments were confirmed by the inhibition of colonic TNF-α production. Moreover, lyophilised microalga or (13S)-HOTE down-regulated cyclo-oxygenase-2 and inducible nitric oxide synthase expression. The present study was the first to show the prophylactic effects of a lyophilised biomass sample of the microalga C. debaryana and the oxylipin (13S)-HOTE on TNBS-induced acute colitis in rats. Our findings suggest that the microalga C. debaryana or derived oxylipins could be used as nutraceuticals in the treatment of the active phase of IBD.

  5. IMMUNE AND METABOLIC DISTURBANCES IN EXPERIMENTAL ACUTE TOXIC HEPATITIS: CORRECTION BY XENOGENIC AND ALLOGENIC HEPATOCYTES

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    A. I. Konoplya

    2016-01-01

    Full Text Available For correspondence: Konoplya Alexander Ivanovich. Address: 3,K. Marx St.,Kursk, 305041,Russian Federation. Tel.: job. (4712 58-81-76; mob. (910 317-87-88. E-mail: konoplya51@mail.ru.Aim. To study the corrective effects of allogeneic and xenogeneic hepatocytes on metabolic disturbances in acute liver toxicity.Material and methods. Investigations were carried out on 75 adult male Wistar rats weighing 120–160 g, 15 rats and 25 mice on the 5–6th days after birth. Acute toxic hepatitis (ATH was modeled by intramuscular injection of carbon tetrachloride at a dose of 3 ml / kg as a 50% solution in olive oil, five times at 24-hour intervals. Isolating xenogeneic (mouse and allogeneic hepatocytes was performed by method of Berry M.N., Friend D.S. The cell suspension was prepared daily and administered at a concentration of 2 × 106 /kg in recipients with ATH intraperitoneally, five times at 24-hour intervals, simultaneously with the first injection of hepatotropic poison.Results. Intoxication by carbon tetrachloride causes development of the biochemical syndromes of liver damage, activation of the functional metabolic activity of peripheral blood neutrophils and free-radical oxidation, breaks intraerythrocytic metabolism. The introduction of allogeneic hepatocytes in recipients with toxic hepatopathy is more efficiently compared with xenogeneic hepatocytes, it corrects local and systemic metabolic disturbances arising due to the impact of hepatotropic poison. Conclusion. Transplantation of xenogenic hepatocytes, and, to a greater extent, of allogenic hepatocytes in ATH conditions is an effective means to restore the functional metabolic activity of hepatocytes, neutrophils and erythrocytes. 

  6. Ultrastructural lesions in the myocardium and kidneys of rabbits in experimental acute Amorimia exotropica poisoning

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    Mauro P. Soares

    2016-03-01

    Full Text Available Abstract: Amorimia exotropica is an important plant associated with sudden death in cattle in Southern Brazil. In order to understand the mechanisms by which A. exotropica causes acute lesions in the heart and kidney of intoxicated animals, an experiment was conducted to determine the histopathology and ultrastructure of myocardial and renal lesions of intoxicated rabbits. After receiving 18g/kg of dried plant, six rabbits died suddenly. At necropsy, the liver was swollen and no other macroscopic lesions were observed. Histologically, centrolobular and midzonal hepatocytes were vacuolated. These vacuoles were strong PAS stained positive, suggesting that they corresponded to glycogen accumulations. In some regions of the ventricular septum and ventricles were found vacuoles of different sizes and the kidneys of two rabbits showed vacuolar degeneration on distal convoluted tubules. Ultrastructurally, the myocardium had cardiomyocytes swelling with separation of myofibrils bundles and rupture and disorganization of the sarcomeres. The mitochondria displayed swelling, disorganization, disruption of the mitochondrial cristae, and electron-dense matrix. Some mitochondria exhibited eccentric projections of their membranes with disruption of both outer and inner membranes. The sarcoplasmic reticulum had no alterations, whereas the T-tubule system was occasionally dilated and ruptured. The kidneys had mitochondrial swelling with disorganization and disruption of the mitochondrial cristae. The vacuoles result from the swelling of the endoplasmatic reticulum and usually were located between two basolateral infoldings and mitochondria, occurring preferentially around the nucleus. The myocytes and T system damages induced by A. exotropica result in acute heart failure and death. Furthermore, this mechanism of cardiotoxicity may be common to all plant containing monofluoroacetate.

  7. Selective cyclooxygenase-2 inhibition protects against myocardial damage in experimental acute ischemia

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    Alberto Carnieto Jr.

    2009-03-01

    Full Text Available BACKGROUND: Acute myocardial infarction is associated with tissue inflammation. Early coronary reperfusion clearly improves the outcome but may help propagate the inflammatory response and enhance tissue damage. Cyclooxygenase-2 is an enzyme that catalyzes the initial step in the formation of inflammatory prostaglandins from arachidonic acid. Cyclooxygenase-2 levels are increased when ischemic cardiac events occur. The overall function of COX-2 in the inflammatory process generated by myocardial ischemic damage has not yet been elucidated. GOAL: The objective of this study was to determine whether a selective cyclooxygenase-2 inhibitor (rofecoxib could alter the evolution of acute myocardial infarction after reperfusion. METHODS AND RESULTS: This study was performed with 48 mongrel dogs divided into two groups: controls and those treated with the drug. All animals were prepared for left anterior descending coronary artery occlusion. The dogs then underwent 180 minutes of coronary occlusion, followed by 30 minutes of reperfusion. Blood samples were collected from the venous sinus immediately before coronary occlusion and after 30 minutes of reperfusion for measurements of CPK-MB, CPK-MBm and troponin I. During the experiment we observed the mean blood pressure, heart rate and coronary flow. The coronary flow and heart rate did not change, but in the control group, there was blood pressure instability, in addition to maximal levels of CPK-MB post-infarction. The same results were observed for CPK-MBm and troponin I. CONCLUSION: In a canine model of myocardial ischemia-reperfusion, selective inhibition of Cyclooxygenase-2 with rofecoxib was not associated with early detrimental effects on the hemodynamic profile or the gross extent of infarction; in fact, it may be beneficial by limiting cell necrosis.

  8. CL 71.366 1-(3-dimetilaminopropil-4-(p. metoxifenil dihidrocloridrato de piperazina no tratamento da doença de Chagas

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    Vanize Macêdo

    1975-10-01

    Full Text Available Os autores trataram 13 indivíduos com a doença de Chagas, 4 na fase aguda e 9 na fase crônica, forma indeterminada, com o CL 71.366 do Laboratório Lederle, usando diferentes esquemas terapêuticos nos dois grupos. Embora a droga fosse relativamente bem suportada pela maioria dos indivíduos, todos os chagásicos, após o tratamento, continuavam com parasitemia demonstrável pelos xenodiagnósticos, apesar do controle de cura não ter sido rigoroso. Concluem os autores pela ineficácia do medicamento no tratamento da doença de Chagas, nos esquemas utilizados.The authors treated 13 individuais with Chagas disease, 4 in the acute phase and 9 in the indeterminate form of the chronic phase with a compound CL 71.366 of Lederle Laboratory. Different dosage schemes for the two groups were used. While the drug was relatively well tolerated by the majority of individuais all the chagasic patients after treatment continued with parasitaemia demonstrable by xenodiagnosis, although the control of cure was not the best. It is concluded that this drug is ineffective in the treatment of Chagas disease in the dosages utilised.

  9. A serological, parasitological and clinical evaluation of untreated Chagas disease patients and those treated with benznidazole before and thirteen years after intervention

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    Girley Francisco Machado-de-Assis

    2013-11-01

    Full Text Available The etiological treatment of Chagas disease is recommended for all patients with acute or recent chronic infection, but controversies remain regarding the benefit of chemotherapy and interpretations of the parasitological cure after etiological treatment. This study compares the laboratory and clinical evaluations of Chagas disease patients who were diagnosed 13 years earlier. Fifty-eight Chagas disease patients (29 treated with benznidazole and 29 untreated were matched at the time of treatment based on several variables. Conventional serology revealed the absence of seroconversion in all patients. However, lower serological titres were verified in the treated group, primarily among patients who had the indeterminate form of the disease. Haemoculture performed 13 years after the intervention was positive for 6.9% and 27.6% of the treated and untreated patients, respectively. Polymerase chain reaction tests were positive for 44.8% and 13.8% of the treated and untreated patients, respectively. Patients who presented with the indeterminate form of the disease at the beginning of the study exhibited less clinical progression (17.4% compared with the untreated group (56.5%. Therefore, this global analysis revealed that etiological treatment with benznidazole may benefit patients with respect to the clinical progression of Chagas disease and the prognosis, particularly when administered to patients with the indeterminate form of the disease.

  10. The proximal effects of acute alcohol use on female aggression: A meta-analytic review of the experimental literature.

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    Crane, Cory A; Licata, MacKenzie L; Schlauch, Robert C; Testa, Maria; Easton, Caroline J

    2017-02-01

    Experimental research on alcohol-related aggression has focused largely upon male participants, providing only a limited understanding of the proximal effects of acute alcohol use on aggression among females extrapolated from the male literature. The current meta-analysis was undertaken to summarize the effects of alcohol, compared to placebo or no alcohol, on female aggression as observed across experimental investigations. A review of the literature yielded 11 articles and 12 effect sizes for further analysis. The overall effect size of alcohol on female aggression was small and reached statistical significance (d = .17, p = .02, 95% confidence interval [.03, .30]). Meta-analytic examination of the experimental literature indicated that alcohol is a significant factor in female aggression. The overall alcohol-aggression effect was smaller than has been observed among male samples. Additional research is required to evaluate the influence of other factors on alcohol-related aggressive responding among female participants. (PsycINFO Database Record (c) 2017 APA, all rights reserved).

  11. Prevention of congenital Chagas through treatment of girls and women of childbearing age

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    Guillermo Moscatelli

    2015-06-01

    Full Text Available It is currently unknown whether treatment of Chagas disease decreases the risk of congenital transmission from previously treated mothers to their infants. In a cohort of women with Chagas disease previously treated with benznidazole, no congenital transmission of the disease was observed in their newborns. This finding provides support for the treatment of Chagas disease as early as possible.

  12. Fotografia e valor documentário: o arquivo de Carlos Chagas Photography and documental value: the Carlos Chagas archive

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    Aline Lopes de Lacerda

    2009-07-01

    Full Text Available Examina questões metodológicas referentes ao tratamento técnico de arquivos, a partir da organização do arquivo de Carlos Chagas. Tendo como objeto as fotografias integrantes dessa documentação, discute a organização arquivística de fotografias e analisa alguns grupos dessas imagens, com enfoque nas fotografias relacionadas à descoberta da doença de Chagas em Lassance. O objetivo é verificar os processos de produção de sentido embutidos na metodologia de classificação desses documentos. Aponta em que medida as imagens relacionadas à estadia de Chagas em Lassance - para onde ele foi inicialmente combater a malária - assumiram novo sentido, diante da importância da descoberta da doença para a sua trajetória e na produção e disseminação de sua memória.Centered on the organization of the Carlos Chagas archive, the article explores methodological concerns in the technical handling of such material. It discusses the archival organization of photographs and analyzes some groups of images from the Chagas archive, particularly photographs concerning the discovery of Chagas' disease, in Lassance, where the scientist initially went to combat malaria. The goal is to identify processes of production of meaning that are built into the methodology for classifying these documents. The article examines to what extent the images of Chagas' stay in Lassance took on new meaning because of the weight this discovery had on the scientist's career and likewise on the production and dissemination of his memory.

  13. Anti-inflammatory and anti-oxidative effects of alpha-lipoic acid in experimentally induced acute otitis media.

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    Tatar, A; Korkmaz, M; Yayla, M; Gozeler, M S; Mutlu, V; Halici, Z; Uslu, H; Korkmaz, H; Selli, J

    2016-07-01

    To investigate the anti-inflammatory, anti-oxidative and tissue protective effects, as well as the potential therapeutic role, of alpha-lipoic acid in experimentally induced acute otitis media. Twenty-five guinea pigs were assigned to one of five groups: a control (non-otitis) group, and otitis-induced groups treated with saline, penicillin G, alpha-lipoic acid, or alpha-lipoic acid plus penicillin G. Tissue samples were histologically analysed, and oxidative parameters in tissue samples were measured and compared between groups. The epithelial integrity was better preserved, and histological signs of inflammation and secretory metaplasia were decreased, in all groups compared to the saline treated otitis group. In the alpha-lipoic acid plus penicillin G treated otitis group, epithelial integrity was well preserved and histological findings of inflammation were significantly decreased compared to the saline, penicillin G and alpha-lipoic acid treated otitis groups. The most favourable oxidative parameters were observed in the control group, followed by the alpha-lipoic acid plus penicillin G treated otitis group. Alpha-lipoic acid, with its antioxidant, anti-inflammatory and tissue protective properties, may decrease the clinical sequelae and morbidity associated with acute otitis media.

  14. The apoptotic effect of a high dose of toluene on liver tissue during the acute phase: an experimental study.

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    Ayan, Murat; Tas, Ufuk; Sogut, Erkan; Kuloglu, Tuncay; Cayli, Sevil; Kocaman, Nevin; Karaca, Zafer Ismail; Sahin, Mehmet

    2013-09-01

    The aim of this study is to investigate the acute toxic effects of high-dose toluene and its mechanisms on the liver tissue of toluene-treated rats. In this study, 16 adult male Wistar albino rats (200-220 g) were divided into two equal groups. Group I was used as a control group, while group II was exposed to high dose of toluene, 5200 mg/kg (6 ml/kg per gavage). After the 3-hour experimental period, blood samples and liver tissues were taken from the euthanized animals. Serum aspartate and alanine aminotransferase levels were assayed. Liver tissues were fixed in 10% neutral formalin, then embedded in paraffin and sectioned (5 μm thickness). Sections were stained with hematoxylin and eosin for histopathological examination. A terminal transferase dUTP nick end labeling assay was also done for the determination of apoptosis in liver tissues. For the determination of Bax and caspase-3 immunoreactivity, the sections were stained using avidin-biotin-peroxidase immunohistochemical method. The level of plasma transaminase was found to be increased in toluene administered rats. Additionally, slight degeneration of hepatocyte and mononuclear cell infiltration was observed in the liver tissue sections and a high (+++) immunoreactivity for Bax and caspase-3 protein was observed in the toluene group. This study showed that the high dose of toluene triggers apoptosis in the liver of rats via the mitochondrial pathway in acute period.

  15. Molecular evolution of GB virus B hepatitis virus during acute resolving and persistent infections in experimentally infected tamarins

    DEFF Research Database (Denmark)

    Takikawa, Shingo; Engle, Ronald E; Faulk, Kristina N

    2010-01-01

    GB virus B (GBV-B) causes acute hepatitis in experimentally infected tamarins. We compared evolutionary features in acute resolving and persistent GBV-B infection. We detected no evidence of evolution in four animals with clearance during weeks 9-12, whereas three animals with clearance during......(-3) substitutions per site year(-1) during weeks 1-52 and 53-104, respectively. Thus, there was a significant decrease in evolution over time, as found for hepatitis C virus. The rate of non-synonymous substitution per non-synonymous site compared with that of synonymous substitution per synonymous site decreased...... weeks 13-26 had several substitutions in their polyprotein sequence. A single tamarin had long-term GBV-B viraemia; analysis of virus recovered at weeks 2, 5, 12, 20, 26, 52 and 104 demonstrated that mutations accumulated over time. Overall, the amino acid substitution rate was 3.5x10(-3) and 1.1x10...

  16. Functional IL18 polymorphism and susceptibility to Chronic Chagas Disease.

    Science.gov (United States)

    Nogueira, Luciana Gabriel; Frade, Amanda Farage; Ianni, Barbara Maria; Laugier, Laurie; Pissetti, Cristina Wide; Cabantous, Sandrine; Baron, Monique; Peixoto, Gisele de Lima; Borges, Ariana de Melo; Donadi, Eduardo; Marin-Neto, José A; Schmidt, André; Dias, Fabrício; Saba, Bruno; Wang, Hui-Tzu Lin; Fragata, Abilio; Sampaio, Marcelo; Hirata, Mario Hiroyuki; Buck, Paula; Mady, Charles; Martinelli, Martino; Lensi, Mariana; Siqueira, Sergio Freitas; Pereira, Alexandre Costa; Rodrigues, Virmondes; Kalil, Jorge; Chevillard, Christophe; Cunha-Neto, Edecio

    2015-05-01

    Chronic Chagas Disease cardiomyopathy (CCC), a life-threatening inflammatory dilated cardiomyopathy, affects 30% of the approximately 8 million patients infected by Trypanosoma cruzi, the rest of the infected subjects remaining asymptomatic (ASY). The Th1 T cell-rich myocarditis plays a pivotal role in CCC pathogenesis. Local expression of IL-18 in CCC myocardial tissue has recently been described. IL-18 could potentially amplify the process by inducing increased expression of IFN-γ which in turn can increase the production of IL-18, thereby creating a positive feedback mechanism. In order to assess the contribution of the IL-18 to susceptibility to Chronic Chagas Disease, we investigated the association between a single nucleotide polymorphism (SNP) located in the IL-18 gene with the risk of developing Chagas cardiomyopathy. We analyzed the rs2043055 marker in the IL18 gene in a cohort of Chagas disease cardiomyopathy patients (n=849) and asymptomatic subjects (n=202). We found a significant difference in genotype frequencies among moderate and severe CCC patients with ventricular dysfunction. Our analysis suggests that the IL18 rs2043055 polymorphism- or a SNP in tight linkage disequilibrium with it- may contribute to modulating the Chagas cardiomyopathy outcome. Copyright © 2015 Elsevier Ltd. All rights reserved.

  17. Epidemiology of Chagas disease in Europe: many calculations, little knowledge.

    Science.gov (United States)

    Strasen, Jörn; Williams, Tatjana; Ertl, Georg; Zoller, Thomas; Stich, August; Ritter, Oliver

    2014-01-01

    Chagas disease and its causative agent Trypanosoma cruzi are endemic in almost all countries in South and Middle America. Currently, there are more than 10 million affected people. It is the most common reason for heart failure and a frequent cause of intestinal problems in Latin America. The phenotype of the Chagas cardiomyopathy is varying. Dilative cardiomyopathy, often accompanied by an apical aneurysm is the most common finding in the end stage heart failure, but rhythm disorders like conduction blocks, ventricular or supraventricular forms of tachycardia or repolarization changes occur as well, mainly in the early stages. Migration of infected people leads to a distribution from the endemic countries to North America and Europe. Although more than 500,000 people of Latin American origin are currently living in Europe, Chagas disease is not considered as a public health problem, yet. Cases of transmission via blood donation, organ transplantation or from mother-to-child are reported for several European countries but there is no database for Germany. Current epidemiological data are mostly available from regional surveys from other countries or are extrapolated. Hence, there is a large variation in the estimated numbers on the incidence of Chagas. Robust and reliable data are lacking. This review gives an overview on the currently available data and calls for a German Chagas surveillance.

  18. The effects of mindful attention and state mindfulness on acute experimental pain among adolescents.

    Science.gov (United States)

    Petter, Mark; McGrath, Patrick J; Chambers, Christine T; Dick, Bruce D

    2014-06-01

    Attention-based coping strategies for pain are widely used in pediatric populations. The purpose of this study was to test a novel mindful attention manipulation on adolescent's experimental pain responses. Furthermore, the relationship between state mindfulness and experimental pain was examined. A total of 198 adolescents were randomly assigned to a mindful attention manipulation or control group prior to an experimental pain task. Participants completed measures of state mindfulness immediately prior to the pain task, and situational catastrophizing and pain intensity following the task. Overall the manipulation had no effect on pain. Secondary analysis showed that meditation experience moderated the effect of the manipulation. State mindfulness predicted pain outcomes, with reductions in situational catastrophizing mediating this relationship. The mindful attention manipulation was effective among adolescents with a regular meditation practice. State mindfulness was related to ameliorated pain responses, and these effects were mediated by reduced catastrophizing. © The Author 2014. Published by Oxford University Press on behalf of the Society of Pediatric Psychology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

  19. Mechanical ventilation guided by electrical impedance tomography in experimental acute lung injury.

    Science.gov (United States)

    Wolf, Gerhard K; Gómez-Laberge, Camille; Rettig, Jordan S; Vargas, Sara O; Smallwood, Craig D; Prabhu, Sanjay P; Vitali, Sally H; Zurakowski, David; Arnold, John H

    2013-05-01

    To utilize real-time electrical impedance tomography to guide lung protective ventilation in an animal model of acute respiratory distress syndrome. Prospective animal study. Animal research center. Twelve Yorkshire swine (15 kg). Lung injury was induced with saline lavage and augmented using large tidal volumes. The control group (n = 6) was ventilated using ARDSnet guidelines, and the electrical impedance tomography-guided group (n = 6) was ventilated using guidance with real-time electrical impedance tomography lung imaging. Regional electrical impedance tomography-derived compliance was used to maximize the recruitment of dependent lung and minimize overdistension of nondependent lung areas. Tidal volume was 6 mL/kg in both groups. Computed tomography was performed in a subset of animals to define the anatomic correlates of electrical impedance tomography imaging (n = 5). Interleukin-8 was quantified in serum and bronchoalveolar lavage samples. Sections of dependent and nondependent regions of the lung were fixed in formalin for histopathologic analysis. Positive end-expiratory pressure levels were higher in the electrical impedance tomography-guided group (14.3 cm H₂O vs. 8.6 cm H₂O; p electrical impedance tomography-guided group (6.9 mL/cm H₂O vs. 4.7 mL/cm H₂O; p = 0.013). Regional electrical impedance tomography-derived compliance of the most dependent lung region was increased in the electrical impedance tomography group (1.78 mL/cm H₂O vs. 0.99 mL/cm H₂O; p = 0.001). Pao₂/FIO₂ ratio was higher and oxygenation index was lower in the electrical impedance tomography-guided group (Pao₂/FIO₂: 388 mm Hg vs. 113 mm Hg, p electrical impedance tomography-guided group (HMEIT 42% samples vs. HMCONTROL 67% samples, p electrical impedance tomography and computed tomography were ± 16%. Electrical impedance tomography-guided ventilation resulted in improved respiratory mechanics, improved gas exchange, and reduced histologic evidence of ventilator

  20. Behavioural biology of Chagas disease vectors

    Directory of Open Access Journals (Sweden)

    Claudio Ricardo Lazzari

    2013-01-01

    Full Text Available Many arthropod species have adopted vertebrate blood as their main food source. Blood is rich in nutrients and, except for the presence of parasites, sterile. However, this food source is not freely available, nor is obtaining it devoid of risk. It circulates inside vessels hidden underneath the skin of mobile hosts that are able to defend themselves and even predate the insects that try to feed on them. Thus, the haematophagous lifestyle is associated with major morphological, physiological and behavioural adaptations that have accumulated throughout the evolutionary history of the various lineages of blood-sucking arthropods. These adaptations have significant consequences for the evolution of parasites as well as for the epidemiology of vector-transmitted diseases. In this review article, we analyse various aspects of the behaviour of triatomine bugs to illustrate how each behavioural trait represents a particular adaptation to their close association with their hosts, which may easily turn into predators. Our aim is to offer to the reader an up-to-date integrative perspective on the behaviour of Chagas disease vectors and to propose new research avenues to encourage both young and experienced colleagues to explore this aspect of triatomine biology.

  1. Differential Expression of Aquaporins in Experimental Models of Acute Lung Injury.

    Science.gov (United States)

    Vassiliou, Alice G; Manitsopoulos, Nikolaos; Kardara, Matina; Maniatis, Nikolaos A; Orfanos, Stylianos E; Kotanidou, Anastasia

    2017-01-01

    The mammalian lung expresses at least three aquaporin (AQP) water channels whose precise role in lung injury or inflammation is still controversial. Three murine models of lung inflammation and corresponding controls were used to evaluate the expression of Aqp1, Aqp4, Aqp5 and Aqp9: lipopolysaccharide (LPS)-induced lung injury; HCl-induced lung injury; and ventilation-induced lung injury (VILI). All models yielded increased lung vascular permeability, and inflammatory cell infiltration in the broncho-alveolar lavage fluid; VILI additionally produced altered lung mechanics. Lung expression of Aqp4 decreased in the models that targeted primarily the alveolar epithelium, i.e. acid aspiration and mechanical ventilation, while Aqp5 expression decreased in the model that appeared to target both the capillary endothelium and alveolar epithelium, i.e. LPS. Participation of aquaporins in the acute inflammatory process depends on localization and the type of lung injury. Copyright© 2017, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.

  2. Chagas Heart Failure in Patients from Latin America.

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    Bestetti, Reinaldo B

    2016-11-01

    Physicians working in Europe and the United States should suspect Chagas heart failure in every patient coming from Latin America with chronic heart failure. Diagnosis should be confirmed by positive serology. Right bundle branch block and left anterior fascicular block on 12-lead electrocardiogram, enlarged cardiac silhouette with no pulmonary congestion on chest X-ray and left ventricular apical aneurysm on echocardiography are the distinctive features of this condition. The clinical course is poorer than that of non-Chagas heart failure; however, medical treatment is similar. Implantable cardioverter-defibrillators are useful in the primary and secondary prevention of sudden cardiac death. Cardiac resynchronisation therapy can be given to patients on optimal medical therapy and with lengthened QRS complex. Heart transplantation is the treatment of choice for patients with end-stage Chagas heart failure.

  3. Central motor conduction in human chronic Chagas' disease

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    M.J. Segura

    1994-03-01

    Full Text Available The possible involvement of spinal alpha motor neurons, dorsal root ganglia and sensory fibers in human chronic Chagas' disease was previously demonstrated. More recently neuropsychological and sensory evoked potentials studies suggest the existence of central nervous system abnormalities in these patients. We assessed the state of central motor pathways in 46 patients with chronic Chagas' disease and 30 healthy volunteers by means of percutaneous cortical and spinal electrical stimulation. No significative slowness in pyramidal tracts (PT conduction was found when comparing both groups. Neither any individual patient exhibited abnormally delayed PT conduction values beyond the upper normal limit of the healthy volunteers. These results suggest that, in contrast with other neural systems, the large myelinated PT fibers are usually spared in human chronic Chagas' disease.

  4. A relationship between proteinuria and acute tubulointerstitial disease in rats with experimental nephrotic syndrome

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    Eddy, A.A.; McCulloch, L.; Liu, E.; Adams, J. (Hospital for Sick Children, Toronto, ON (Canada))

    1991-05-01

    The relationship between tubulointerstitial nephritis and proteinuria was characterized in experimental nephrosis in rats. In one group, proteinuria induced by aminonucleoside of puromycin (PAN) was reduced by using an 8% protein diet and adding the angiotensin I-converting enzyme (ACE) inhibitor enalapril to the drinking water. Two control groups were injected with saline and PAN, respectively, and fed a 27% protein diet. The first group had significantly reduced albuminuria and a definite attenuation of tubular cell injury. There was a strong positive correlation between the number of interstitial macrophages and albuminuria. The beneficial effect was reproduced by dietary-protein restriction alone, whereas ACE inhibition alone had an insignificant effect on the degree of proteinuria. Depletion of circulating T lymphocytes in one group of nephrotic rats eliminated interstitial lymphocytes but did not affect interstitial macrophage influx. Inhibition of the in situ proliferation of resident interstitial macrophages by unilateral kidney irradiation failed to change the intensity of the macrophage infiltration. Treatment of rats with sodium maleate produced proximal tubular cell toxicity but interstitial inflammation did not develop, suggesting that the latter is not a nonspecific response to tubular injury. These studies demonstrate a strong relationship between tubulointerstitial nephritis and the severity of proteinuria in experimental nephrosis.

  5. Acutely damaged axons are remyelinated in multiple sclerosis and experimental models of demyelination.

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    Schultz, Verena; van der Meer, Franziska; Wrzos, Claudia; Scheidt, Uta; Bahn, Erik; Stadelmann, Christine; Brück, Wolfgang; Junker, Andreas

    2017-08-01

    Remyelination is in the center of new therapies for the treatment of multiple sclerosis to resolve and improve disease symptoms and protect axons from further damage. Although remyelination is considered beneficial in the long term, it is not known, whether this is also the case early in lesion formation. Additionally, the precise timing of acute axonal damage and remyelination has not been assessed so far. To shed light onto the interrelation between axons and the myelin sheath during de- and remyelination, we employed cuprizone- and focal lysolecithin-induced demyelination and performed time course experiments assessing the evolution of early and late stage remyelination and axonal damage. We observed damaged axons with signs of remyelination after cuprizone diet cessation and lysolecithin injection. Similar observations were made in early multiple sclerosis lesions. To assess the correlation of remyelination and axonal damage in multiple sclerosis lesions, we took advantage of a cohort of patients with early and late stage remyelinated lesions and assessed the number of APP- and SMI32- positive damaged axons and the density of SMI31-positive and silver impregnated preserved axons. Early de- and remyelinating lesions did not differ with respect to axonal density and axonal damage, but we observed a lower axonal density in late stage demyelinated multiple sclerosis lesions than in remyelinated multiple sclerosis lesions. Our findings suggest that remyelination may not only be protective over a long period of time, but may play an important role in the immediate axonal recuperation after a demyelinating insult. © 2017 The Authors GLIA Published by Wiley Periodicals, Inc.

  6. The Costs of Preventing and Treating Chagas Disease in Colombia

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    Castillo-Riquelme, Marianela; Guhl, Felipe; Turriago, Brenda; Pinto, Nestor; Rosas, Fernando; Martínez, Mónica Flórez; Fox-Rushby, Julia; Davies, Clive; Campbell-Lendrum, Diarmid

    2008-01-01

    Background The objective of this study is to report the costs of Chagas disease in Colombia, in terms of vector disease control programmes and the costs of providing care to chronic Chagas disease patients with cardiomyopathy. Methods Data were collected from Colombia in 2004. A retrospective review of costs for vector control programmes carried out in rural areas included 3,084 houses surveyed for infestation with triatomine bugs and 3,305 houses sprayed with insecticide. A total of 63 patient records from 3 different hospitals were selected for a retrospective review of resource use. Consensus methodology with local experts was used to estimate care seeking behaviour and to complement observed data on utilisation. Findings The mean cost per house per entomological survey was $4.4 (in US$ of 2004), whereas the mean cost of spraying a house with insecticide was $27. The main cost driver of spraying was the price of the insecticide, which varied greatly. Treatment of a chronic Chagas disease patient costs between $46.4 and $7,981 per year in Colombia, depending on severity and the level of care used. Combining cost and utilisation estimates the expected cost of treatment per patient-year is $1,028, whereas lifetime costs averaged $11,619 per patient. Chronic Chagas disease patients have limited access to healthcare, with an estimated 22% of patients never seeking care. Conclusion Chagas disease is a preventable condition that affects mostly poor populations living in rural areas. The mean costs of surveying houses for infestation and spraying infested houses were low in comparison to other studies and in line with treatment costs. Care seeking behaviour and the type of insurance affiliation seem to play a role in the facilities and type of care that patients use, thus raising concerns about equitable access to care. Preventing Chagas disease in Colombia would be cost-effective and could contribute to prevent inequalities in health and healthcare. PMID:19015725

  7. The costs of preventing and treating chagas disease in Colombia.

    Science.gov (United States)

    Castillo-Riquelme, Marianela; Guhl, Felipe; Turriago, Brenda; Pinto, Nestor; Rosas, Fernando; Martínez, Mónica Flórez; Fox-Rushby, Julia; Davies, Clive; Campbell-Lendrum, Diarmid

    2008-01-01

    The objective of this study is to report the costs of Chagas disease in Colombia, in terms of vector disease control programmes and the costs of providing care to chronic Chagas disease patients with cardiomyopathy. Data were collected from Colombia in 2004. A retrospective review of costs for vector control programmes carried out in rural areas included 3,084 houses surveyed for infestation with triatomine bugs and 3,305 houses sprayed with insecticide. A total of 63 patient records from 3 different hospitals were selected for a retrospective review of resource use. Consensus methodology with local experts was used to estimate care seeking behaviour and to complement observed data on utilisation. The mean cost per house per entomological survey was $4.4 (in US$ of 2004), whereas the mean cost of spraying a house with insecticide was $27. The main cost driver of spraying was the price of the insecticide, which varied greatly. Treatment of a chronic Chagas disease patient costs between $46.4 and $7,981 per year in Colombia, depending on severity and the level of care used. Combining cost and utilisation estimates the expected cost of treatment per patient-year is $1,028, whereas lifetime costs averaged $11,619 per patient. Chronic Chagas disease patients have limited access to healthcare, with an estimated 22% of patients never seeking care. Chagas disease is a preventable condition that affects mostly poor populations living in rural areas. The mean costs of surveying houses for infestation and spraying infested houses were low in comparison to other studies and in line with treatment costs. Care seeking behaviour and the type of insurance affiliation seem to play a role in the facilities and type of care that patients use, thus raising concerns about equitable access to care. Preventing Chagas disease in Colombia would be cost-effective and could contribute to prevent inequalities in health and healthcare.

  8. Chagas disease in the State of Amazonas: history, epidemiological evolution, risks of endemicity and future perspectives.

    Science.gov (United States)

    Barbosa, Maria das Graças Vale; Ferreira, João Marcos Bemfica Barbosa; Arcanjo, Ana Ruth Lima; Santana, Rosa Amélia Gonçalves; Magalhães, Laylah Kelre Costa; Magalhães, Laise Kelma Costa; Mota, Daniel Testa; Fé, Nelson Ferreira; Monteiro, Wuelton Marcelo; Silveira, Henrique; Guerra, Jorge Augusto de Oliveira

    2015-01-01

    Chagas disease (CD) is a parasitic infection that originated in the Americas and is caused by Trypanosoma cruzi. In the last few years, the disease has spread to countries in North America, Asia and Europe due to the migration of Latin Americans. In the Brazilian Amazon, CD has an endemic transmission, especially in the Rio Negro region, where an occupational hazard was described for piaçaveiros (piassaba gatherers). In the State of Amazonas, the first chagasic infection was reported in 1977, and the first acute CD case was recorded in 1980. After initiatives to integrate acute CD diagnostics with the malaria laboratories network, reports of acute CD cases have increased. Most of these cases are associated with oral transmission by the consumption of contaminated food. Chronic cases have also been diagnosed, mostly in the indeterminate form. These cases were detected by serological surveys in cardiologic outpatient clinics and during blood donor screening. Considering that the control mechanisms adopted in Brazil's classic transmission areas are not fully applicable in the Amazon, it is important to understand the disease behavior in this region, both in the acute and chronic cases. Therefore, the pursuit of control measures for the Amazon region should be a priority given that CD represents a challenge to preserving the way of life of the Amazon's inhabitants.

  9. Chagas disease in the State of Amazonas: history, epidemiological evolution, risks of endemicity and future perspectives

    Directory of Open Access Journals (Sweden)

    Maria das Graças Vale Barbosa

    2015-06-01

    Full Text Available Chagas disease (CD is a parasitic infection that originated in the Americas and is caused by Trypanosoma cruzi. In the last few years, the disease has spread to countries in North America, Asia and Europe due to the migration of Latin Americans. In the Brazilian Amazon, CD has an endemic transmission, especially in the Rio Negro region, where an occupational hazard was described for piaçaveiros (piassaba gatherers. In the State of Amazonas, the first chagasic infection was reported in 1977, and the first acute CD case was recorded in 1980. After initiatives to integrate acute CD diagnostics with the malaria laboratories network, reports of acute CD cases have increased. Most of these cases are associated with oral transmission by the consumption of contaminated food. Chronic cases have also been diagnosed, mostly in the indeterminate form. These cases were detected by serological surveys in cardiologic outpatient clinics and during blood donor screening. Considering that the control mechanisms adopted in Brazil's classic transmission areas are not fully applicable in the Amazon, it is important to understand the disease behavior in this region, both in the acute and chronic cases. Therefore, the pursuit of control measures for the Amazon region should be a priority given that CD represents a challenge to preserving the way of life of the Amazon's inhabitants.

  10. Experimental validation of contrast-enhanced SSFP cine CMR for quantification of myocardium at risk in acute myocardial infarction.

    Science.gov (United States)

    Nordlund, David; Kanski, Mikael; Jablonowski, Robert; Koul, Sasha; Erlinge, David; Carlsson, Marcus; Engblom, Henrik; Aletras, Anthony H; Arheden, Håkan

    2017-01-30

    Accurate assessment of myocardium at risk (MaR) after acute myocardial infarction (AMI) is necessary when assessing myocardial salvage. Contrast-enhanced steady-state free precession (CE-SSFP) is a recently developed cardiovascular magnetic resonance (CMR) method for assessment of MaR up to 1 week after AMI. Our aim was to validate CE-SSFP for determination of MaR in an experimental porcine model using myocardial perfusion single-photon emission computed tomography (MPS) as a reference standard and to test the stability of MaR-quantification over time after injecting gadolinium-based contrast. Eleven pigs were subjected to either 35 or 40 min occlusion of the left anterior descending artery followed by six hours of reperfusion. A technetium-based perfusion tracer was administered intravenously ten minutes before reperfusion. In-vivo and ex-vivo CE-SSFP CMR was performed followed by ex-vivo MPS imaging. MaR was expressed as % of left ventricular mass (LVM). There was good agreement between MaR by ex-vivo CMR and MaR by MPS (bias: 1 ± 3% LVM, r 2  = 0.92, p myocardial salvage in experimental studies.

  11. Serological diagnosis of Chagas disease in HIV-infected patients

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    Dulce Stauffert

    2015-06-01

    Full Text Available INTRODUCTION: This study assessed the rate of request for the serological diagnosis of Chagas disease among human immunodeficiency virus (HIV-infected patients treated at the Specialized Care Service of Pelotas, Rio Grande do Sul, Brazil. METHODS: This cross-sectional study used secondary data obtained from the medical records of 252 patients aged between 18 and 75 years. RESULTS: The serological diagnosis of Chagas disease was requested only in 3.2% of cases. CONCLUSIONS: The results demonstrate poor adherence to protocols on the part of healthcare professionals, indicating the need to reevaluate the procedures applied to HIV-infected patients from endemic regions for both diseases.

  12. Congenital Chagas disease as an ecological model of interactions between Trypanosoma cruzi parasites, pregnant women, placenta and fetuses.

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    Carlier, Yves; Truyens, Carine

    2015-11-01

    The aim of this paper is to discuss the main ecological interactions between the parasite Trypanosoma cruzi and its hosts, the mother and the fetus, leading to the transmission and development of congenital Chagas disease. One or several infecting strains of T. cruzi (with specific features) interact with: (i) the immune system of a pregnant woman whom responses depend on genetic and environmental factors, (ii) the placenta harboring its own defenses, and, finally, (iii) the fetal immune system displaying responses also susceptible to be modulated by maternal and environmental factors, as well as his own genetic background which is different from her mother. The severity of congenital Chagas disease depends on the magnitude of such final responses. The paper is mainly based on human data, but integrates also complementary observations obtained in experimental infections. It also focuses on important gaps in our knowledge of this congenital infection, such as the role of parasite diversity vs host genetic factors, as well as that of the maternal and placental microbiomes and the microbiome acquisition by infant in the control of infection. Investigations on these topics are needed in order to improve the programs aiming to diagnose, manage and control congenital Chagas disease. Copyright © 2015 The Authors. Published by Elsevier B.V. All rights reserved.

  13. Aspectos neurológicos da moléstia de chagas Neurological aspects of Chagas disease

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    Fritz Köberle

    1967-09-01

    Full Text Available Carlos Chagas related in more than two 200 cases, what he called "nervous forms" of trypanosomiasis, that is neurological manifestations from central origin (idiotism, infantilism, pseudo-bulbar paralysis, aphasia, cerebellar ataxia, atetosis, espostic or paralytic diplegia, disbasia. At that time Chagas expressed his concepts as follows: "In relation to the frequency of trypanosomiasis nervous forms we have performed many observations which allow us to state that this disease is the one which causes the largest number of organic affections of the central nervous system, in human pathology". We are plenty convinced by Chagas's statement. By experiments on animals of laboratory we have very often noticed a rather varied neurological symptomatology, being worth point out identical syndromes to those observed by Chagas. Our autopsy material non-rarely include chronic Chagas cases presenting a most varied symtomatology. Among them we have named only three cases of discerebral nanism, a rather rare affection in other parts of the world and relatively frequent in our material. The fact which we have demonstrated, i.e., a relatively great decreasing of number of nervous cells in the peripheral system could happen in the central nervous system as well. Provided that there are only two quantitative works on neuron number diminishing in the central nervous system in mice and rats we decline to go into further details about central neuropathies in man. We emphasized the necessity to perform researches on this field by means of intimate collaboration between clinicians and pathologists, as the only way to confirm on scientific basis all that was observed by the panoramic and genial vision of Carlos Chagas.

  14. Melatonin exacerbates acute experimental autoimmune encephalomyelitis by enhancing the serum levels of lactate: A potential biomarker of multiple sclerosis progression.

    Science.gov (United States)

    Ghareghani, Majid; Dokoohaki, Shima; Ghanbari, Amir; Farhadi, Naser; Zibara, Kazem; Khodadoust, Saeid; Parishani, Mohammad; Ghavamizadeh, Mehdi; Sadeghi, Heibatollah

    2017-01-01

    Melatonin has a beneficial role in adult rat models of multiple sclerosis (MS). In this study, melatonin treatment (10 mg/kg/d) was investigated in young age (5-6 weeks old) Lewis rat model of acute experimental autoimmune encephalomyelitis (EAE) followed by assessing serum levels of lactate and melatonin. Results showed that clinical outcomes were exacerbated in melatonin- (neurological score = 6) vs PBS-treated EAE rats (score = 5). Melatonin caused a significant increase in serum IFN-γ, in comparison to PBS-treated EAE rats whereas no considerable change in IL-4 levels were found, although they were significantly lower than those of controls. The ratio of IFN-γ/IL-4, an indicator of Th-1/Th-2, was significantly higher in PBS- and melatonin- treated EAE rats, in comparison to controls. Moreover, results showed increased lymphocyte infiltration, activated astrocytes (GFAP+ cells) but also higher demyelinated plaques (MBP-deficient areas) in the lumbar spinal cord of melatonin-treated EAE rats. Finally, serum levels of lactate, but not melatonin, significantly increased in the melatonin group, compared to untreated EAE and normal rats. In conclusion, our results indicated a relationship between age and the development of EAE since a negative impact was found for melatonin on EAE recovery of young rats by enhancing IFN-γ, the ratio of Th1/Th2 cells, and astrocyte activation, which seems to delay the remyelination process. While melatonin levels decline in MS patients, lactate might be a potential diagnostic biomarker for prediction of disease progression. Early administration of melatonin in the acute phase of MS might be harmful and needs further investigations. © 2016 John Wiley & Sons Australia, Ltd.

  15. Experimental infection of commercial layers using a Salmonella enterica serovar Gallinarum strain: Leukogram and serum acute-phase protein concentrations

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    KO Garcia

    2009-12-01

    Full Text Available The aim of the present study was to evaluate white blood cell counts and serum protein profiles of commercial layers experimentally infected with Salmonella Gallinarum (SG in order to better understand the pathophysiology of the disease caused by this bacterium. 180 five-day-old commercial layers were divided into 3 groups (G; G1 and G2 received 0.2 mL of inoculate containing 3.3x10(8 CFU or 3.3x10(5 CFU SG resistant to nalidix acid (Nal r/mL, respectively, directly into their crops. G3 group did not receive the inoculum. Birds were sacrificed 24 hours before (T1 and 24 hours after the infection (T2, and three (T3, five (T4, seven (T5, and ten (T6 days after the administration of the inoculum. White blood cell counts were carried out in a Neubauer hemocytometer and in blood smears. Serum protein concentrations, including acute-phase proteins, were determined using sodium dodecyl sulphate-polyacrylamide gel electrophoresis (SDS-PAGE. Data were submitted to analysis of variance, and means were compared by Tukey's test (P <0.05. G1 and G2 groups presented higher leukocyte counts on T4 and T5, respectively, due to the increase of circulating lymphocytes and heterophils, with a significant difference relative to G3. In electrophoresis, an increase in the serum levels of ceruloplasmin, haptoglobin, and hemopexin and a decrease in transferrin, which are acute-phase proteins, was verified. IgA serum levels did not change; however, IgG concentration increased during the infection. In conclusion, the results provide information for the better understanding of the pathophysiology of fowl typhoid.

  16. Effect of propolis versus metronidazole and their combined use in treatment of acute experimental giardiasis.

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    Abdel-Fattah, Nashwa S; Nada, Ola H

    2007-08-01

    Propolis, a honey bee product, gained popularity in alternative medicine. Its prophylactic and therapeutic effects were experimentally evaluated. One hundred and fifty immunocompetent mice were orally infected by 5 x 10(5) axenically cultivated Giardia lamblia trophozoites. The trophozoite count in intestine, interferon-gamma serum level, histopathological examination of duodenal and jejunal sections were assessed for evaluation of propolis and metronidazole (MTZ) effect after 6 & 12 days post infection (p.i). Also, T-lymphocyte profile in blood was investigated 12 days p.i using flow cytometry (FCM). Propolis as prophylaxis showed a significant decrease in intensity of infection, together with a significant increase in IF-gamma serum level and increase in CD4+: CD8+T-cell ratio. In treatment it gave a highly significant decrease in trophozoite count than that obtained by MTZ 6 days after infection but the efficacy was almost equal after 12 days. The mice treated with propolis alone showed a reversed CD4+: CD8+ T-lymphocyte ratio, such strong immune enhancing effect resulted in an undesirable increase in inflammatory response at intestinal level. The combined therapy showed a stronger efficacy in reducing the parasite count than that gained by each drug alone. Their combined use caused an immunological balance as shown by the T-lymphocyte profile that saved the intestinal homeostasis and histological architecture.

  17. NSAIDs in the Acute Treatment of Migraine: A Review of Clinical and Experimental Data

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    Arpad Pardutz

    2010-06-01

    Full Text Available Migraine is a common disabling neurological disorder with a serious socio-economical burden. By blocking cyclooxygenase nonsteroidal anti-inflammatory drugs (NSAIDs decrease the synthesis of prostaglandins, which are involved in the pathophysiology of migraine headaches. Despite the introduction more than a decade ago of a new class of migraine-specific drugs with superior efficacy, the triptans, NSAIDs remain the most commonly used therapies for the migraine attack. This is in part due to their wide availability as over-the-counter drugs and their pharmaco-economic advantages, but also to a favorable efficacy/side effect profile at least in attacks of mild and moderate intensity. We summarize here both the experimental data showing that NSAIDs are able to influence several pathophysiological facets of the migraine headache and the clinical studies providing evidence for the therapeutic efficacy of various subclasses of NSAIDs in migraine therapy. Taken together these data indicate that there are several targets for NSAIDs in migraine pathophysiology and that on the spectrum of clinical potency acetaminophen is at the lower end while ibuprofen is among the most effective drugs. Acetaminophen and aspirin excluded, comparative trials between the other NSAIDs are missing. Since evidence-based criteria are scarce, the selection of an NSAID should take into account proof and degree of efficacy, rapid GI absorption, gastric ulcer risk and previous experience of each individual patient. If selected and prescribed wisely, NSAIDs are precious, safe and cost-efficient drugs for the treatment of migraine attacks.

  18. Effect of Induced Mild Hypothermia on Acid-Base Balance During Experimental Acute Sepsis in Rats.

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    Léon, Karelle; Pichavant-Rafini, Karine; Ollivier, Hélène; L'Her, Erwan

    2015-09-01

    The aim of this study was to determine the effect of induced mild hypothermia (34°C) on acid-base balance in septic rats. Twenty-eight male Sprague-Dawley rats median weight 306 g, range 251-333 g were used. After anesthesia and when the target temperature was reached (normothermia: 38°C or induced mild hypothermia: 34°C), sepsis was induced by cecal ligation and perforation. Measurements of cardiopulmonary parameters and blood samples were performed at T0h (occurring immediately after chirurgical procedures), T2h, T4h (at each temperature), and T6h (at 34°C only). Blood oxygen saturation, heart and respiratory rates, arterial blood pH, carbon dioxide partial pressure, sodium, potassium, chloride and calcium concentrations, hematocrit, blood lactate, tumor necrosis factor-α and interleukin-6 concentrations were measured on anesthetized rats. Other parameters such as bicarbonate concentration, hemoglobin concentration, base excess, and anion gap were estimated from measured parameters. Main results showed that an increase in both cytokines concentrations was observed in septic rats compared with sham rats. This increase was less marked at 34°C compared with 38°C. Moreover, sepsis induction led to a marked metabolic acidosis and hypothermia delayed this acidosis. Induced mild hypothermia delays the evolution of cytokines and metabolic acidosis during experimental sepsis.

  19. Cytokine production profile of heart-infiltrating T cells in Chagas' disease cardiomyopathy

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    Cunha-Neto E.

    1998-01-01

    Full Text Available The hallmark of chronic Chagas' disease cardiomyopathy (CCC is the finding of a T cell-rich inflammatory mononuclear cell infiltrate in the presence of extremely few parasites in the heart lesions. The scarcity of parasites in affected heart tissue casts doubt on the direct participation of Trypanosoma cruzi in CCC heart tissue lesions, and suggests the possible involvement of autoimmunity. The cells in the infiltrate are presumably the ultimate effectors of tissue damage, and there is evidence that such cells recognize cardiac myosin in molecular mimicry with T. cruzi proteins rather than primary reactivity to T. cruzi antigens (Cunha-Neto et al. (1996 Journal of Clinical Investigation, 98: 1709-1712. Recently, we have studied heart-infiltrating T cells at the functional level. In this short review we summarize the studies about the role of cytokines in human and experimental T. cruzi infection, along with our data on heart-infiltrating T cells in human Chagas' cardiomyopathy. The bulk of evidence points to a significant production of IFN-g and TNF-a which may be linked to T. cruzi-induced IL-12 production

  20. Do Brazilian scientific journals promote the adherence of Chagas disease researchers to international ethical principles?

    Science.gov (United States)

    Malafaia, Guilherme; Guilhem, Dirce; Talvani, André

    2013-01-01

    The ethical aspects of the Brazilian publications about human Chagas disease (CD) developed between 1996 and 2010 and the policy adopted by Brazilian medical journals were analyzed. Articles were selected on the SciELO Brazil data basis, and the evaluation of ethical aspects was based on the normative contents about ethics in research involving human experimentation according to the Brazilian resolution of the National Health Council no. 196/1996. The editorial policies of the section "Instructions to authors" were analyzed. In the period of 1996-2012, 58.9% of articles involving human Chagas disease did not refer to the fulfillment of the ethical aspects concerning research with human beings. In 80% of the journals, the requirements and confirmation of the information about ethical aspects in the studies of human CD were not observed. Although a failure in this type of service is still observed, awareness has been raised in federal agencies, educational institutions/research and publishing groups to standardize the procedures and ethical requirements for the Brazilian journals, reinforcing the fulfillment of the ethical parameters, according to the resolution of NHC no. 196/1996.

  1. Do Brazilian scientific journals promote the adherence of Chagas disease researchers to internacional ethical principals?

    Directory of Open Access Journals (Sweden)

    Guilherme Malafaia

    2013-06-01

    Full Text Available The ethical aspects of the Brazilian publications about human Chagas disease (CD developed between 1996 and 2010 and the policy adopted by Brazilian medical journals were analyzed. Articles were selected on the SciELO Brazil data basis, and the evaluation of ethical aspects was based on the normative contents about ethics in research involving human experimentation according to the Brazilian resolution of the National Health Council no. 196/1996. The editorial policies of the section "Instructions to authors" were analyzed. In the period of 1996-2012, 58.9% of articles involving human Chagas disease did not refer to the fulfillment of the ethical aspects concerning research with human beings. In 80% of the journals, the requirements and confirmation of the information about ethical aspects in the studies of human CD were not observed. Although a failure in this type of service is still observed, awareness has been raised in federal agencies, educational institutions/research and publishing groups to standardize the procedures and ethical requirements for the Brazilian journals, reinforcing the fulfillment of the ethical parameters, according to the resolution of NHC no. 196/1996.

  2. EXPERIMENTAL ACUTE NEPHRITIS: THE VASCULAR REACTIONS AND THE ELIMINATION OF NITROGEN

    Science.gov (United States)

    Pearce, Richard M.; Hill, Miner C.; Eisenbrey, Arthur B.

    1910-01-01

    By combining physiological and anatomical methods in the study of experimental nephritis it is possible to distinguish types of nephritis in which either tubular or vascular changes predominate, and are essentially characteristic of the lesion produced, but it is not possible to say that a given poison produces exclusively tubular or exclusively vascular lesions. The so-called epithelial poisons (potassium chromate, uranium nitrate and corrosive sublimate) present anatomical evidence of extensive tubular injury, and in the early stages show, on physiological study, no evidence of vascular injury other than exaggerated contraction and dilatation of the vessels and increased diuresis. On the other hand, the vascular poisons, arsenic and cantharidin, which produce but little injury to the tubules, tend to cause anuria and are characterized by minimal contraction and dilatation of the vessels and little or no flow of urine. From the physiological point of view these two types may be, for practical purposes, considered as examples of tubular and vascular nephritis. They are not, however, pure types; for the increased diuresis of the early tubular type is in itself evidence of vessel irritability and similar to the increased irritability caused by small doses of vascular poisons, and on the other hand, this essentially vascular lesion is accompanied by slight morphological changes in the tubular epithelium. Furthermore, the tubular lesions of chromium and uranium and corrosive sublimate pass into a stage closely resembling the vascular type, if not identical with it. Two forms of late tubular nephritis may be recognized. One of these, the anuric form, is accompanied by severe gastro-intestinal disturbance and evidence of approaching anuria; physiological tests show diminished power of dilatation of the vessels and corresponding inhibition of diuresis. The second form, the polyuric, is characterized by a condition of polyuria up to the moment of anesthesia; physiological

  3. Research on acute and chronic toxity of the experimental drug Аmprolinsyl

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    B. Gutyj

    2017-02-01

    membranes of hepatocytes, which indicates increased activity of aminotransferases.When investigating the chronic toxicity of Amprolinsyl it was found that at doses of 1/50 LD50, and 1/100 LD50 the drug had no effect on the results of functional tests, due to the normal functioning of the liver tissue and the lack of negative impact on animals in the 3rd and 4th groups. Administration of the the drug at doses of 1/20, 1/50 and 1/100 LD50 over 30 days did not significantly affect the functional state of the internal organs of the experimental animals. When investigating the morphological blood parameters of the rats following oral administration of Amprolinsyl at different doses a downward trend in the haemoglobin and colour index value and a likely reduction in the number of white blood cells, compared to the control group was observed in all experimental groups. According to the values of haematological and biochemical parameters, it was established that in spite of the low toxicityof Amprolinsyl at doses of 1/20 and 1/50 LD50 the drug had an effect on lipid metabolism, as was shown following the increase of glycerol.

  4. Efeito da prednisona em lesão medular aguda experimental em ratos Effect of prednisone on acute experimental spinal cord injury in rats

    Directory of Open Access Journals (Sweden)

    C.M.O. Silva

    2008-06-01

    Full Text Available Foram utilizados 25 ratos (Rattus novergicus submetidos a trauma experimental da medula espinhal, empregando-se aparelho estereotáxico com um peso de 50,5g comprimindo a duramáter durante cinco minutos. Após o trauma, os animais foram divididos em cinco grupos de cinco. O grupo A (controle recebeu placebo oito horas após o trauma; os grupos B, C, D e E receberam prednisona oito, 24, 48 e 120 horas após o trauma, respectivamente. A prednisona foi administrada na dose inicial de 2mg/kg, durante cinco dias, com diminuição progressiva até o 26º dia. Os animais foram avaliados conforme a capacidade motora, posicionamento proprioceptivo, reflexo de localização, plano inclinado e sensibilidade dolorosa. Após 33 dias da cirurgia, foram sacrificados para avaliação histológica das medulas espinhais. Observaram-se degeneração das raízes nervosas, necrose medular, inflamação local e reação glial, sem diferenças entre os grupos. Não houve correlação entre os testes neurológicos. A utilização da prednisona na lesão medular aguda não teve efeito diferenciado com o tempo e não foi prejudicial na recuperação neurológica, mesmo quando utilizada tardiamente.Twent-five rats (Rattus novergicus were submitted to an experimental spinal cord injury by using a 50.5g stereotaxic equipament to apply pressure on the duramater during five minutes. After the spinal cord injury, the animals were randomly distributed into five groups of five animals each: one group received placebo 8 hours after injury and the remaining four groups received prednisone at 8, 24, 48, and 120 hours after injury. Prednisone was applied at 2mg/kg dosage during five days and progressively reduced until the 26th day. Animals were evaluated by motor capacity, proprioceptive positioning, locating reflex, inclined plan, and sensibility to pain. The animals were sacrificed 33 days after surgery for histological study of the spinal cords that revealed degeneration of the

  5. [Histopathological and autoradiographical studies of experimental brain tumors after continuous local chemotherapy--acute stage in rat models].

    Science.gov (United States)

    Shimura, T; Teramoto, A; Aihara, K

    1997-04-01

    Continuous local chemotherapy has been evaluated as being an effective administration method and as a possible adjuvant therapy in the sensitivity aspect of the cell cycle for malignant glioma. However, neurotoxicity of anti-cancer agents in the normal brain and non-effective methods for the deeper part of the tumor seem to be the most serious problems. This study was initiated to evaluate histological findings, the uptake distribution, and neurotoxicity of the continuous local administration of isotope labeled anti-cancer agents in the brain tumor of rats. The experimental brain tumor of rats and the method of continuous local chemotherapy were as follows. The tumor was produced by intracerebral inoculation of cultured cells derived from rat brain tumor induced by Rous sarcoma virus (Kumanishi et al. strain). One week later Fluorouracil (5-6-3H) (17.7 Ci/m mol) and methotrexate (L-glutamyl 3-4-3H) (41.0 Ci/m mol) were administered into the brain tumors of rats utilizing a mini osmotic pump (Alzet Model 2001), respectively. We used five rats of various groups. The rats were sacrificed at various time intervals (6 hrs, 12 hrs, 24 hrs, 48 hrs, 72 hrs and 7 days). The tumor tissues for light microscopic autoradiography were fixed in 10% formalin for 24 hours. Sections for the light microscopic autoradiography were cut at 4 mu thick and coated with Sakura NR-M2 drips. Following exposure for one week at 4 degrees C, the sections were stained with Konidol X. Six hours after administration, slight radioactivity was distributed in the subarachnoid space and subpial brain tissue in the vicinity of the inserted tube. Twenty-four hours after administration, high radioactivity was clearly present in many tumor cells and phagocytes at the tube tip, but no radioactivity was observed in the deeper part of the tumor or normal brain tissue. In the vicinity of necrosis foci, acute toxic inflammation was also observed. In conclusion, this experimental study shows that these anti

  6. Doença de Chagas no Brasil Chagas disease in Brazil

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    Márcio C. Vinhaes

    2000-01-01

    Full Text Available Sumariam-se os dados da Fundação Nacional de Saúde (FNS sobre o estado atual dos vetores da doença de Chagas no Brasil, verificando-se que após vinte anos de controle químico continuado houve franca redução dos índices triatomínico-tripanosômicos, particularmente para esp��cies como Triatoma infestans e Panstrongylus megistus. Em paralelo, dados de sorologia escolar, de internações e de mortalidade pela doença indicam descenso nas taxas de incidência e impacto médico social da protozoose, restando áreas mais preocupantes, como o Nordeste e resíduos de T. infestans. Impõe-se urgente uma vigilância epidemiológica efetiva, a ser realizada por estados e municípios ante o processo de descentralização da FNS.This article presents the current situation for Chagas disease vectors in Brazil, based on data from the Brazilian National Health Foundation (FNS. Over the course of the last 20 years, continuous chemical control has resulted in a clear reduction of triatomine densities and Trypanosoma cruzi in Brazilian dwellings. Results have been particularly promising in relation to Triatoma infestans and Panstrongylus megistus, considered the most important species in the past. In parallel, data from school serological surveys, hospitalized patients, and mortality records show an important decrease in the disease. Nevertheless, some areas of the Brazilian Northeast and some residual foci of Triatoma infestans and Panstrongylus megistus remain as major challenges for public health authorities, requiring effective epidemiological surveillance. States and municipalities are required to assume this task at present, as the traditional Brazilian National Health Foundation is undergoing decentralization.

  7. Enfermedad de Chagas congenita en la Ciudad de Salta, Argentina Congenital Chagas' disease in Salta, Argentina

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    Mario Zaidenberg

    1993-02-01

    Full Text Available Se estudió la respuesta clínica y serológica a la infección chagásica de 937 embarazadas y sus 929 recién nacidos (RN vivos, grupo I; 4 RN de origen diverso, grupo II y 35 RN derivados de otros centros, grupo III. Las embarazadas se estudiaron con 3 reacciones serológicas; se definió infección cuando 2 o más reacciones eran positivas. En los RN el diagnóstico se confirmó por observación directa del T. cruzi en una muestra de sangre. Los RN con Chagas congénita (RN-ChC fueron tratados y seguidos con estudios clínicos y de laboratorio. Se detectaron 149 embarazadas chagásicas (15.9%, de las cuales se diagnosticaron 6 RN-ChC (4%. En el total de 968 RN estudiados se detectaron 12 RN infectados. El micro-hematócrito fue el método parasitológico de lectura rápida más efectivo para el diagnóstico de infección en nuestra serie. El par de reacciones serológicas específicas constituyó un criterio de mayor seguridad para el control y seguimiento de la infección congénita. Las expresiones clínicas más comunes de infección fueron hepatomegalia, esplenomegalia, ictericia, anemia y prematurez, con distintos grados de asociación. Se concluye que dadas las características clínicas de la enfermedad de Chagas congénita en nuestro medio, se impone como estrategia el diagnóstico serológico para la enfermedad de Chagas en todas las embarazadas y el control y seguimiento de sus RN hasta descartar o confirmar infección congénita.The immune response to Trypanosoma cruzi was studied in our hospital in 937 pregnant women (PW and their 929 newborns (NB, group I; 4 NB from this center not included in the first group, group II and 35 NB derived from other centers, group III. Two positive results among indirect hemagglutination (IHA, complement fixation (CF and indirect hemagglutination (IHA, complement fixation (CF and indirect immunofluorescence (IIF tests were considered as the criterion of previous infection with T. cruzi in PW. The

  8. [Biological and non-biological elimination therapy of acute liver failure. Experimental study on large laboratory animal].

    Science.gov (United States)

    Ryska, M; Lásziková, E; Pantoflícek, T; Kieslichová, E; Ryska, O; Prazák, J; Koblihová, E; Skibová, J

    2008-01-01

    Development of biological and non-biological artificial liver devices in the previous 20 years enabled effective treatment of acute liver failure (ALF) of patients waiting for liver transplantation or for spontaneous liver parenchyma regeneration. Aim of the study was the evaluation of the effectiveness of biological (BAL - bioartificial liver) and non-biological (FPSA - Fractionated plasma separation and adsorption) methods in the treatment of experimental ALF on large laboratory animal. Surgical model of ALF with liver devascularization in pigs (weight 25-40 kg) was provided following monitoring of ALF markers (AST, ALT, bilirubin, ammoniac, glycaemia, INR) including intracranial pressure (ICP). Control group included animals without treatment of ALF. Results of both experimental groups were compared and statistically worked-out with that of controls by T-test and Mann-Whitney non-parametric test by EXCEL and QUATRO. BAL group: 10 pigs (weight 30 +/- 5 kg) with ALF were treated by BAL with isolated hepatocytes. When plasma bilirubin was compared, significant differences (p < 0.05) in 6 and 9 hours interval were found favouring BAL group (18.1 vs. 13.1, 22.9 vs. 13.2 mmol/l). The value of ICP in both groups was no significant. Prometheus group: 14 pigs weight 35 kg (35 +/- 5 kg) with the identical ALF were treated by Prometheus (FPSA). Level of serum bilirubin in experimental group when compared to control group was significantly lower (p < 0.01) at 6 hour interval 12.81 +/- 6.54 vs. 29.84 +/- 9.99 at 9 hour 11.94 +/- 4.14 vs. 29.95 +/- 12.36 and at 12 hour 13.88 +/- 6.31 vs. 26.10 +/- 12.23 mmol/l. No significant difference in serum ammonia level was found. ICP was significantly different from 9 hour to 12 hour interval in favour of FPSA group (p < 0.01): 9 hour 19.1 +/- 4.09 vs. 24.1 +/- 2.85, 10 hour 21.9 +/- 3.63 vs. 25.1 +/- 2.19, 11 hour 22.5 +/- 3.98 vs. 26.3 +/- 3.50 and 12 hour 24.0 +/- 4.66 vs. 29.8 +/- 5.88 mm Hg. Significant improvement of bilirubin

  9. Preventing Chagas in Central America through simple home ...

    International Development Research Centre (IDRC) Digital Library (Canada)

    2016-05-05

    May 5, 2016 ... In about one-third of those infected, the parasites lodge in the heart and digestive muscle, and can ultimately lead to heart failure and sudden death. As a chronic disease affecting mainly those in poverty, Chagas weighs heavily on the economies and health systems in areas where it is widespread. With no ...

  10. Tackling Chagas disease in Central America | IDRC - International ...

    International Development Research Centre (IDRC) Digital Library (Canada)

    2012-06-07

    Jun 7, 2012 ... ... the native species soon return. Early symptoms of Chagas tend to be relatively minor — fever, aches and pains, and localized swelling — and many people will not realize they have acquired a serious disease. Years later, the disease can cause chronic and even fatal heart and gastrointestinal problems.

  11. MICROCIRCULATION AND CHAGAS' DISEASE: HYPOTHESIS AND RECENT RESULTS

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    RAMOS Simone G.

    1999-01-01

    Full Text Available This review focuses on studies that support the microvascular hypothesis, as well as on immunological and neurogenic mechanisms, and the role of the parasite itself, to explain further the pathology and clinical course of myocardial involvement in chagasic cardiomyopathy. The salient features of coronary microcirculation and Chagas' disease are discussed.

  12. Ecohealth Interventions for Chagas Disease Prevention in Central ...

    International Development Research Centre (IDRC) Digital Library (Canada)

    Chagas disease is a important vector-borne disease that constitutes a significant burden of illness among the poor in Latin America and the Caribbean (LAC). More than 10 million people in the region are infected by the parasite Trypanosoma Cruzi. About one third will develop the chronic phase of the disease, leading to ...

  13. Honduras stands out in fight against chagas disease | IDRC ...

    International Development Research Centre (IDRC) Digital Library (Canada)

    2011-01-25

    Jan 25, 2011 ... Education first. Previous research showed that Chagas primarily affects the rural poor. In San Franciso de Opalaca, poverty is widespread: 92% of its 9 000 residents live in extreme poverty and have limited access to potable water or electricity. Among children under five years old, malnourishment is a ...

  14. Chagas. From Exotic Tropical Disease to Pathology Globalized

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    Beatriz BASSO

    2016-09-01

    Full Text Available Chagas disease, whose aetiological agent is Trypanosoma cruzi, is one of the main endemic diseases in Latin America, ranking fourth regarding the number of lost life years due to death or disability in the area; nevertheless, it is among the so-called “neglected diseases”. Despite its rural origin, where it is transmitted through vector insects belonging to the Reduviidae family, it has nowadays also become a problem in urbanized areas and is becoming globalized through inter-human transmission, above all congenital, but also through transfusions and transplants. Chagas, a Hidden Affliction (Chagas, Un mal escondido, a documentary by Ricardo Preve, focuses on both aspects of the disease: the rural and the global one, including interviews with North American doctors and European researchers. A significant part of the film takes place in the USA, showing the worst consequence of the evolution of the disease, which is death by chagasic cardiopathy which, being a reality that takes place during filming, increases the sense of drama. In this paper we approach specific topics related to Chagas disease from a biomedical point of view, including comments related to the highlights of the film that are connected with such aspects. Towards the end, there is mention of the film Houses of Fire (Casas de fuego and of certain illustrative aspects concerning the life of Dr Salvador Mazza and the Argentine Mission of Regional Pathology Studies (MEPRA, topics that have already been dealt with in this. 

  15. Ecohealth Interventions for Chagas Disease Prevention in Central ...

    International Development Research Centre (IDRC) Digital Library (Canada)

    Extrants. Rapports. Intervenciones en ECOSALUD para la prevención de la enfermedad de Chagas en América Central : informe final correspondiente al periodo del 1 de marzo 2011 al 31 de marzo 2014. Matériels de formation. Manuales (para publicar por PNUD y el de JICA Nicaragua, El Salvador con PRESANCA) ...

  16. Chagas cardiomyopathy in the context of the chronic disease transition.

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    Alicia I Hidron

    2010-05-01

    Full Text Available Patients with Chagas disease have migrated to cities, where obesity, hypertension and other cardiac risk factors are common.The study included adult patients evaluated by the cardiology service in a public hospital in Santa Cruz, Bolivia. Data included risk factors for T. cruzi infection, medical history, physical examination, electrocardiogram, echocardiogram, and contact 9 months after initial data collection to ascertain mortality. Serology and PCR for Trypanosoma cruzi were performed. Of 394 participants, 251 (64% had confirmed T. cruzi infection by serology. Among seropositive participants, 109 (43% had positive results by conventional PCR; of these, 89 (82% also had positive results by real time PCR. There was a high prevalence of hypertension (64% and overweight (body mass index [BMI] >25; 67%, with no difference by T. cruzi infection status. Nearly 60% of symptomatic congestive heart failure was attributed to Chagas cardiomyopathy; mortality was also higher for seropositive than seronegative patients (p = 0.05. In multivariable models, longer residence in an endemic province, residence in a rural area and poor housing conditions were associated with T. cruzi infection. Male sex, increasing age and poor housing were independent predictors of Chagas cardiomyopathy severity. Males and participants with BMI Chagas cardiomyopathy remains an important cause of congestive heart failure in this hospital population, and should be evaluated in the context of the epidemiological transition that has increased risk of obesity, hypertension and chronic cardiovascular disease.

  17. Proteomic profile of circulating immune complexes in chronic Chagas disease.

    Science.gov (United States)

    Ohyama, K; Huy, N T; Yoshimi, H; Kishikawa, N; Nishizawa, J E; Roca, Y; Revollo Guzmán, R J; Velarde, F U G; Kuroda, N; Hirayama, K

    2016-10-01

    Immune complexes (ICs) are the direct and real-time products of humoral immune responses. The identification of constituent foreign or autoantigens within ICs might bring new insights into the pathology of infectious diseases. We applied immune complexome analysis of plasma to the study of Chagas disease caused by Trypanosoma cruzi. Twenty seropositive plasma samples including cardiac and/or megacolon determinate patients (n = 11) and indeterminate (n = 9) were analysed along with 10 seronegative individuals to characterize the antigens bound to circulating ICs. We identified 39 T. cruzi antigens and 114 human autoantigens specific to patients with Chagas. Among those antigens, two T. cruzi antigens (surface protease GP63, glucose-6-isomerase) and six human autoantigens (CD180 antigen, ceruloplasmin, fibrinogen beta chain, fibrinogen beta chain isoform 2 preprotein, isoform gamma-A of fibrinogen γ-chain, serum paraoxonase) were detected in more than 50% of the patients tested. Human isoform short of complement factor H-related protein 2 and trans-sialidase of T. cruzi were more frequently found in the indeterminate (5/9 for both) compared with in the determinate Chagas (0/11, P = 0·046 for human, 1/11, P = 0·0498 for T. cruzi). The immune complexome could illustrate the difference of immune status between clinical forms of chronic Chagas disease. © 2016 John Wiley & Sons Ltd.

  18. Estimating the Burden of Chagas Disease in the United States.

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    Jennifer Manne-Goehler

    2016-11-01

    Full Text Available In recent years, there has been growing awareness of the significant burden of Chagas disease in the United States (US. However, epidemiological data on both prevalence and access to care for this disease are limited. The objective of this study is to provide an updated national estimate of Chagas disease prevalence, the first state-level estimates of cases of T. cruzi infection in the US and to analyze these estimates in the context of data on confirmed cases of infection in the US blood supply.In this study, we calculated estimates of the state and national prevalence of Chagas disease. The number of residents originally from Chagas disease endemic countries were computed using data on Foreign-Born Hispanic populations from the American Community Survey, along with recent prevalence estimates for Chagas disease in Latin America from the World Health Organization that were published in 2006 and updated in 2015. We then describe the distribution of estimated cases in each state in relation to the number of infections identified in the donated blood supply per data from the AABB (formerly American Association of Blood Banks.The results of this analysis offer an updated national estimate of 238,091 cases of T. cruzi infection in the United States as of 2012, using the same method as was used by Bern and Montgomery to estimate cases in 2005. This estimate indicates that there are 62,070 cases less than the most recent prior estimate, though it does not include undocumented immigrants who may account for as many as 109,000 additional cases. The state level results show that four states (California, Texas, Florida and New York have over 10,000 cases and an additional seven states have over 5,000 cases. Moreover, since 2007, the AABB has reported 1,908 confirmed cases of T. cruzi infection identified through screening of blood donations.This study demonstrates a substantial burden of Chagas disease in the US, with state variation that reflects the

  19. Estimating the Burden of Chagas Disease in the United States

    Science.gov (United States)

    Manne-Goehler, Jennifer; Umeh, Chukwuemeka A.; Montgomery, Susan P.; Wirtz, Veronika J.

    2016-01-01

    Background In recent years, there has been growing awareness of the significant burden of Chagas disease in the United States (US). However, epidemiological data on both prevalence and access to care for this disease are limited. The objective of this study is to provide an updated national estimate of Chagas disease prevalence, the first state-level estimates of cases of T. cruzi infection in the US and to analyze these estimates in the context of data on confirmed cases of infection in the US blood supply. Methods In this study, we calculated estimates of the state and national prevalence of Chagas disease. The number of residents originally from Chagas disease endemic countries were computed using data on Foreign-Born Hispanic populations from the American Community Survey, along with recent prevalence estimates for Chagas disease in Latin America from the World Health Organization that were published in 2006 and updated in 2015. We then describe the distribution of estimated cases in each state in relation to the number of infections identified in the donated blood supply per data from the AABB (formerly American Association of Blood Banks). Findings The results of this analysis offer an updated national estimate of 238,091 cases of T. cruzi infection in the United States as of 2012, using the same method as was used by Bern and Montgomery to estimate cases in 2005. This estimate indicates that there are 62,070 cases less than the most recent prior estimate, though it does not include undocumented immigrants who may account for as many as 109,000 additional cases. The state level results show that four states (California, Texas, Florida and New York) have over 10,000 cases and an additional seven states have over 5,000 cases. Moreover, since 2007, the AABB has reported 1,908 confirmed cases of T. cruzi infection identified through screening of blood donations. Conclusions This study demonstrates a substantial burden of Chagas disease in the US, with state

  20. Estimating the Burden of Chagas Disease in the United States.

    Science.gov (United States)

    Manne-Goehler, Jennifer; Umeh, Chukwuemeka A; Montgomery, Susan P; Wirtz, Veronika J

    2016-11-01

    In recent years, there has been growing awareness of the significant burden of Chagas disease in the United States (US). However, epidemiological data on both prevalence and access to care for this disease are limited. The objective of this study is to provide an updated national estimate of Chagas disease prevalence, the first state-level estimates of cases of T. cruzi infection in the US and to analyze these estimates in the context of data on confirmed cases of infection in the US blood supply. In this study, we calculated estimates of the state and national prevalence of Chagas disease. The number of residents originally from Chagas disease endemic countries were computed using data on Foreign-Born Hispanic populations from the American Community Survey, along with recent prevalence estimates for Chagas disease in Latin America from the World Health Organization that were published in 2006 and updated in 2015. We then describe the distribution of estimated cases in each state in relation to the number of infections identified in the donated blood supply per data from the AABB (formerly American Association of Blood Banks). The results of this analysis offer an updated national estimate of 238,091 cases of T. cruzi infection in the United States as of 2012, using the same method as was used by Bern and Montgomery to estimate cases in 2005. This estimate indicates that there are 62,070 cases less than the most recent prior estimate, though it does not include undocumented immigrants who may account for as many as 109,000 additional cases. The state level results show that four states (California, Texas, Florida and New York) have over 10,000 cases and an additional seven states have over 5,000 cases. Moreover, since 2007, the AABB has reported 1,908 confirmed cases of T. cruzi infection identified through screening of blood donations. This study demonstrates a substantial burden of Chagas disease in the US, with state variation that reflects the distribution of

  1. The value of combined elevation of D-dimer and neopterin as a predictive parameter for early stage acute mesenteric ischemia: An experimental study.

    Science.gov (United States)

    Coskun, Ali Kagan; Halici, Zekai; Oral, Akgun; Bayir, Yasin; Deniz, Ferhat; Caycı, Tuncer; Mentes, Oner; Oz, Bilgehan Savas; Harlak, Ali; Yigit, Taner; Kozak, Orhan; Peker, Yusuf

    2017-04-01

    Background The diagnosis of acute mesenteric ischemia is variable. Early diagnosis is important for reducing the mortality and morbidity rates. Aim This experimental study aims to investigate the diagnostic utility of D-dimer and neopterin as a marker for the early stage of acute mesenteric ischemia caused by occlusion of superior mesenteric artery. Methods The levels of D-dimer and neopterin were measured using an animal acute mesenteric ischemia model in 21 male rabbits. Superior mesenteric artery occlusion (Group 1, n = 14) and control (Group 2, n = 7) groups were identified. Blood samples at different times are collected from each rabbits. Blood samples from superior mesenteric artery occlusion group were taken 30 min after anesthesia but before laparotomy, 1, 2, and 3 h after superior mesenteric artery ligation. Blood samples from control group were taken 1 h before, 1 and 3 h after anesthesia and laparotomy. The D-dimer and neopterin levels of each blood sample were measured. Results The probability of acute mesenteric ischemia was found to be 36 times higher when the D-dimer level was over 0.125 ng/L, whereas the probability was 19.2 times higher when the neopterin level was over 1.25 nmol/L. Conclusions In this experimental study, the combined elevation of two significant markers, D-dimer and neopterin, may be helpful for the early diagnosis of acute mesenteric ischemia.

  2. Myocardial motion and deformation patterns in an experimental swine model of acute LBBB/CRT and chronic infarct.

    Science.gov (United States)

    Duchateau, Nicolas; Sitges, Marta; Doltra, Adelina; Fernández-Armenta, Juan; Solanes, Nuria; Rigol, Montserrat; Gabrielli, Luigi; Silva, Etelvino; Barceló, Aina; Berruezo, Antonio; Mont, Lluís; Brugada, Josep; Bijnens, Bart

    2014-06-01

    In cardiac resynchronization therapy (CRT), specific changes in motion/deformation happen with left-bundle-branch-block (LBBB) and following treatment. However, they remain sub-optimally studied. We propose a two-fold improvement of their characterization. This includes controlling them through an experimental model and using more suitable quantification techniques. We used a swine model of acute LBBB and CRT with/without chronic infarct (pure-LBBB: N = 11; LBBB + left-anterior-descending infarct: N = 11). Myocardial displacement, velocity and strain were extracted from short-axis echocardiographic sequences using 2D speckle-tracking. The data was transformed to a single spatiotemporal system of coordinates to perform subject comparisons and quantify pattern changes at similar locations and instants. Pure-LBBB animals showed a specific intra-ventricular dyssynchrony pattern with LBBB (11/11 animals), and the recovery towards a normal pattern with CRT (10/11 animals). Pattern variability was low within the pure-LBBB population, as quantified by our method. This was not correctly assessed by more conventional measurements. Infarct presence affected the pattern distribution and CRT efficiency (improvements in 6/11 animals). Pattern changes correlated with global cardiac function (global circumferential strain) changes in all the animals (corrected: (pLBBBvsBaseline) < 0.001, (pCRTvsBaseline) = NS; non-corrected: (pLBBBvsBaseline) = NS, (pCRTvsBaseline) = 0.028). Our LBBB/CRT experimental model allowed controlling specific factors responsible for changes in mechanical dyssynchrony and therapy. We illustrated the importance of our quantification method to study these changes and their variability. Our findings confirm the importance of myocardial viability and of specific LBBB-related mechanical dyssynchrony patterns.

  3. [Multidetector-row CT evaluation of acute bowel ischemia induced by embolization of superior mesenteric artery in experimental porcine models].

    Science.gov (United States)

    Qiang, Jin-wei; Li, Ruo-kun; Feng, Xiao-yuan; Liao, Zhi-he; He, Cheng; Feng, Qin; Zhang, Biao; Ye, Xuan-guang

    2010-02-01

    To evaluate the application of multi-detector row CT (MDCT) and CT angiography (CTA) for detecting early signs of acute bowel ischemia (ABI) in experimental porcine models. Twelve pigs were assigned to four groups with 3 in each group. The digital subtraction angiography of superior mesenteric artery (SMA) and the embolization of branches of SMA with gelatin sponge and blood clot were performed by percutaneous transfemoral artery puncture and catheterization. MDCT pre- and post-contrast scanning in the arterial, venous and delay phase and CTA with three-dimensional reconstruction were carried out at pre-operation, 3 h, 6 h, 9 h, and 12 h after occlusion. The normal mesenteric vascular anatomy, arterial occlusion, mesentery and bowel changes, and dynamic change were evaluated. ABI changes were identified pathologically in all the 12 experimental pigs, and the severity of ischemia increased over time after embolization. CTA showed all 57 embolized branches of SMA and 29 of 34 unoccluded arterial branches with 5 false-positive vessel occlusions. The sensitivity and specificity of CTA were 100% and 85.3%, respectively. Thin-slab maximum intensity projection (TSMIP) revealed the disappearance of distal comb-like vessel branches and brush-like vasa recta, which were clearly delineated in the normal bowel segments. Using this criterion, TSMIP correctly defined 23 of 24 ischemic bowel segments and all the 12 normal bowel segments with a sensitivity of 95.8% and a specificity of 100%. MDCT and CTA reliably define normal and occluded mesenteric vessels in the pig. It can easily detect ischemic bowel segment by identified early changes of ischemia. The early direct ischemic signs are occluded vessels, the disappearance of distal comb-like branches or brush-like vasa recta, and poor bowel enhancement. The early indirect sign is bowel dilatation with fluid collection.

  4. Zanthoxylum chiloperone leaves extract: first sustainable Chagas disease treatment.

    Science.gov (United States)

    Ferreira, Maria Elena; Cebrián-Torrejón, Gerardo; Corrales, Alba Segovia; Vera de Bilbao, Ninfa; Rolón, Miriam; Gomez, Celeste Vega; Leblanc, Karine; Yaluf, Gloria; Schinini, Alicia; Torres, Susana; Serna, Elva; Rojas de Arias, Antonieta; Poupon, Erwan; Fournet, Alain

    2011-02-16

    for 70 days. The mutagenic and cytotoxic activity of the main component of Zanthoxylum chiloperone, canthin-6-one, by mouse bone marrow micronucleus test. Canthin-6-one was the main compound of stem and root bark and 5-methoxy-canthin-6-one in leaves and fruits. The ethanolic leaves extract, canthin-6-one and benznidazole presented, approximately, the same level of in vitro activity against trypomastigote and amastigote forms of Trypanosoma cruzi. We have also evaluated the mutagenic and cytotoxic effects of canthin-6-one by micronucleus test in mice. This test showed any mutagenic and cytotoxic damages. The effects of oral or subcutaneous treatments at 10 mg/kg daily for 2 weeks with the ethanolic extract of leaves of Zanthoxylum chiloperone were examined in Balb/c mice infected acutely with Trypanosoma cruzi (CL or Y strain) and compared with benznidazole at 50 mg/kg for 2 weeks. In these experiments, 70 days after infection, parasitaemia and serological response were significantly reduced with the oral ethanolic extract treatment compared with reference drug. This study have shown the efficacy of the leaves extract of Zanthoxylum chiloperone in reducing Trypanosoma cruzi parasitaemia in vivo assays and could be welcomed by scientific and rural communities of Paraguay because it could help them towards the use of local resources to treat an endemic infection, Chagas disease, affecting 20% of the population of this country. Copyright © 2010 Elsevier Ireland Ltd. All rights reserved.

  5. Clinicopathological features and immunohistochemical detection of antigens in acute experimental Streptococcus agalactiae infection in red tilapia (Oreochromis spp.).

    Science.gov (United States)

    Abdullah, Syuhaidah; Omar, Noraini; Yusoff, Sabri Mohd; Obukwho, Emikpe Benjamin; Nwunuji, Tanko Polycarp; Hanan, Latifah; Samad, Jamil

    2013-01-01

    This study investigates the clinicopathological features of acute experimental streptococcosis in red tilapia using various routes of infection; intraperitoneal (IP), immersion (IM) and immersion cut (IC). Twenty four red tilapia in duplicates were inoculated intraperitoneally with 10(9) CFU/ml of S. agalactiae while another sets: intact, one with sharp cut at the tail end were exposed to bacterial inoculums 10(9) CFU/ml diluted in water while two groups of control fish were similarly manipulated. Clinical signs were recorded; samples from the gills, brain, eyes and kidneys were also taken for bacterial isolation and histopathology. Immunohistochemistry (IHC) and polymerase chain reaction (PCR) were employed to detect the antigen. The diseased fish showed skin, fin haemorrhages and exophthalmia with obvious signs in IP at 2 hpc followed by IC and IM at 4 hpc. The lesions were noticed earlier in the kidney and most severe in IP. IHC detected antigen as early as PCR and isolation with intense staining in blood vessel lumen and wall, macrophages in choroid, focal haemorrhage in the renal interstitium and meninges especially in IP followed by IC and IM. The immunolocalisation of the antigen described for the first time further explain the pathogenesis of streptococcosis in red tilapia.

  6. Detection of parenchymal abnormalities in experimentally induced acute pyelonephritis in rabbits using contrast-enhanced ultrasonography, CT, and MRI

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    Ryu, Jeong Ah; Kim, Bo Hyun; Kim, Seung Kwon; Seo, Jin Won [Dept. of Radiology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul (Korea, Republic of); Kim, Jong Sung [Laboratory Animal Research Center, Samsung Biomedical Research Institute, Sungkyunkwan University School of Medicine, Seoul (Korea, Republic of)

    2016-12-15

    We evaluated the efficacy of contrast-enhanced ultrasonography (CEUS) in detecting acute pyelonephritis (APN) using the rabbit kidney model and compared it with CT and MRI. This study was approved by the Institutional Review Board. In a total of 20 New Zealand White rabbits, APN was induced experimentally. CEUS, CT, and MRI were performed on the first, third, and seventh postoperative days. After imaging studies, the subjects were sacrificed and the pathological diagnosis of APN was confirmed in each animal by a pathologist. Imaging studies were obtained in eight animals, including eight CEUS, four computed tomography (CT), and four magnetic resonance imaging (MRI) images. CEUS depicted diffuse renal enlargement (7), diffuse heterogeneous parenchymal enhancement (6), and focal areas of decreased parenchymal enhancement (6). These findings were well correlated with the CT and MRI findings in five cases in which these studies were available. CT and MRI showed diffuse renal enlargement, diffuse heterogeneous parenchymal enhancement, focal areas of decreased parenchymal enhancement, focal contour bulging, and the finding of perinephric spread of infection. In a rabbit model, CEUS could depict the parenchymal lesions of APN similar to CT or MRI; however, it was limited in depicting the perinephric extension of inflammation.

  7. Left ventricular wall motion in patients with Chagas's disease.

    Science.gov (United States)

    Hammermeister, K E; Caeiro, T; Crespo, E; Palmero, H; Gibson, D G

    1984-01-01

    The effect of early chronic Chagas's disease on the timing and extent of regional left ventricular wall motion was studied with a frame by frame analysis of left ventriculograms in nine patients and compared with those in 19 normal subjects. In all the patients there was hypokinesis or akinesis in the anteroapical region together with delay in the onset of inward movement. Hypokinesis of the proximal inferior segment was also present, but the time of onset of inward motion here was normal. These differences can be explained on the basis of regional asynchrony within the normal left ventricle, where anteroapical wall motion is delayed with respect to that elsewhere. Thus contraction of the diseased anteroapical segment starts against an appreciable pressure and so may be isometric, whereas the affected proximal inferior segment starts contracting earlier against a lower pressure and so is able to shorten. No abnormalities of wall motion were seen during isovolumic relaxation despite segmental involvement, which is a distinctly different finding from that in patients with coronary artery disease. This may be due partly to the absence of incoordinate relaxation in Chagas's disease and partly to myocardial involvement by Chagas's disease in the mid-anterior segment. This is the site of rapid early diastolic wall thinning, which has been put forward as a major mechanism of normal rapid ventricular filling and whose premature activity causes disturbances in regional wall motion before mitral valve opening when relaxation is incoordinate. Thus quantitative analysis of both the timing and amplitude of wall motion indicates fundamental differences between Chagas's disease and coronary artery disease, when a less complex analysis would have shown a similar pattern of segmental dysfunction in both. Since the effect of the same pathological process on wall motion varies with the site of ventricular involvement, the importance of the disturbances seen in Chagas's disease

  8. Inflammatory and Cardiac Biomarkers are Differentially Expressed in Chagas Disease

    Science.gov (United States)

    Keating, SM; Deng, X; Fernandes, F; Cunha-Neto, E; Ribeiro, AL; Adesina, B; Beyer, AI; Contestable, P; Custer, B; Busch, MP; Sabino, EC

    2016-01-01

    Background Chagas disease has a long clinically silent period following Trypanosoma cruzi infection and before development of overt clinical pathology; detectable biomarkers of infection and pathogenesis are urgently needed. We tested 22 biomarkers known to be associated with cardiomyopathy to evaluate if a biomarker signature could successfully classify T. cruzi seropositive subjects into clinical Chagas disease stage groups. Methods This cross-sectional retrospective case-control study enrolled T. cruzi seropositive blood donors (BD) that were further characterized as having chronic Chagas cardiomyopathy (CC-BD) or not (nonCC-BD) and seronegative (SN) control donors; we also included clinically diagnosed Chagas cardiomyopathy (CC-P). All subjects underwent a health history questionnaire, medical examination, electro- and echocardiograms (ECG and Echo) and phlebotomy. Biomarkers were measured on blinded samples by luminex bead array and Ortho VITROS. Results A clear biomarker pattern was observed only in more severe cardiac disease; this pattern included significantly elevated levels of inflammatory cytokines IFN-γ IL-6, IL-10 and TNF-α and soluble cardiovascular disease biomarkers CK-MB, troponin, myoglobin, VCAM and NTproBNP while there were lower levels of MPO, PAI-1, and MCP-1. The markers determined to be most predictive of disease by ROC curve analysis were NTproBNP and T. cruzi PCR status. Conclusions Although many biomarkers demonstrated increased or decreased concentrations among the clinical forms of Chagas disease, NTproBNP and T. cruzi PCR were the only tests that would independently be of clinical value for disease staging, in concert with ECG, Echo and clinical assessments. PMID:26277551

  9. Chagas disease in a Texan horse with neurologic deficits.

    Science.gov (United States)

    Bryan, Laura K; Hamer, Sarah A; Shaw, Sarah; Curtis-Robles, Rachel; Auckland, Lisa D; Hodo, Carolyn L; Chaffin, Keith; Rech, Raquel R

    2016-01-30

    A 10-year-old Quarter Horse gelding presented to the Texas A&M University Veterinary Teaching Hospital with a six month-history of ataxia and lameness in the hind limbs. The horse was treated presumptively for equine protozoal myeloencephalitis (EPM) based on clinical signs but was ultimately euthanized after its condition worsened. Gross lesions were limited to a small area of reddening in the gray matter of the thoracic spinal cord. Histologically, trypanosome amastigotes morphologically similar to Trypanosoma cruzi, the agent of Chagas disease in humans and dogs, were sporadically detected within segments of the thoracic spinal cord surrounded by mild lymphoplasmacytic inflammation. Ancillary testing for Sarcocystis neurona, Neospora spp., Toxoplasma gondii and Leishmania spp. was negative. Conventional and real time polymerase chain reaction (PCR) of affected paraffin embedded spinal cord were positive for T. cruzi, and sequencing of the amplified T. cruzi satellite DNA PCR fragment from the horse was homologous with various clones of T. cruzi in GenBank. While canine Chagas disease cases have been widely reported in southern Texas, this is the first report of clinical T. cruzi infection in an equid with demonstrable amastigotes in the spinal cord. In contrast to previous instances of Chagas disease in the central nervous system (CNS) of dogs and humans, no inflammation or T. cruzi amastigotes were detected in the heart of the horse. Based on clinical signs, there is a potential for misdiagnosis of Chagas disease with other infectious diseases that affect the equine CNS. T. cruzi should be considered as a differential diagnosis in horses with neurologic clinical signs and histologic evidence of meningomyelitis that originate in areas where Chagas disease is present. The prevalence of T. cruzi in horses and the role of equids in the parasite life cycle require further study. Copyright © 2015 Elsevier B.V. All rights reserved.

  10. Current drug therapy and pharmaceutical challenges for Chagas disease.

    Science.gov (United States)

    Bermudez, José; Davies, Carolina; Simonazzi, Analía; Real, Juan Pablo; Palma, Santiago

    2016-04-01

    One of the most significant health problems in the American continent in terms of human health, and socioeconomic impact is Chagas disease, caused by the protozoan parasite Trypanosoma cruzi. Infection was originally transmitted by reduviid insects, congenitally from mother to fetus, and by oral ingestion in sylvatic/rural environments, but blood transfusions, organ transplants, laboratory accidents, and sharing of contaminated syringes also contribute to modern day transmission. Likewise, Chagas disease used to be endemic from Northern Mexico to Argentina, but migrations have earned it global. The parasite has a complex life cycle, infecting different species, and invading a variety of cells - including muscle and nerve cells of the heart and gastrointestinal tract - in the mammalian host. Human infection outcome is a potentially fatal cardiomyopathy, and gastrointestinal tract lesions. In absence of a vaccine, vector control and treatment of patients are the only tools to control the disease. Unfortunately, the only drugs now available for Chagas' disease, Nifurtimox and Benznidazole, are relatively toxic for adult patients, and require prolonged administration. Benznidazole is the first choice for Chagas disease treatment due to its lower side effects than Nifurtimox. However, different strategies are being sought to overcome Benznidazole's toxicity including shorter or intermittent administration schedules-either alone or in combination with other drugs. In addition, a long list of compounds has shown trypanocidal activity, ranging from natural products to specially designed molecules, re-purposing drugs commercialized to treat other maladies, and homeopathy. In the present review, we will briefly summarize the upturns of current treatment of Chagas disease, discuss the increment on research and scientific publications about this topic, and give an overview of the state-of-the-art research aiming to produce an alternative medication to treat T. cruzi infection

  11. Community-Based Entomological Surveillance Reveals Urban Foci of Chagas Disease Vectors in Sobral, State of Ceará, Northeastern Brazil.

    Science.gov (United States)

    Parente, Cynara Carvalho; Bezerra, Fernando S M; Parente, Plutarco I; Dias-Neto, Raimundo V; Xavier, Samanta C C; Ramos, Alberto N; Carvalho-Costa, Filipe A; Lima, Marli M

    2017-01-01

    The aim of this work was to explore the potential risk of vector-borne Chagas disease in urban districts in northeastern Brazil, by analyzing the spatiotemporal distributions and natural infection rates with Trypanosoma cruzi of triatomine species captured in recent years. The main motivation of this work was an acute human case of Chagas disease reported in 2008 in the municipality of Sobral. We analyzed data from community-based entomological surveillance carried out from 2010 to 2014. Triatomine natural T. cruzi infection was assessed by examination of insect feces by optical microscopy. Sites of triatomine capture were georeferenced through Google Earth and analyzed with ArcGIS. A total of 191 triatomines were collected, consisting of 82.2% Triatoma pseudomaculata, 7.9% Rhodnius nasutus, 5.8% T. brasiliensis, 3.7% Panstrongylus lutzi, and 0.5% P. megistus, with an overall natural infection index of 17.8%. Most infestations were reported in the districts of Dom José (36.2%), Padre Palhano (24.7%), and Alto do Cristo (10.6%). The overwhelming majority of insects (185/96.9%) were captured inside houses, and most insects tended to be collected in intermittent peaks. Moreover, captured triatomines tended to constitute colonies. The acute case reported in 2008 was found to be situated within a T. pseudomaculata hotspot. The triatomine collection events carried out by dwellers were aggregated in time and space into distinct foci, suggesting that insects are intermittently and artificially introduced into the city, possibly via accidental migration from their natural reservoirs. The relatively high T. cruzi infection rate indicates considerable circulation of the parasite in these areas, increasing the risk of vector-borne Chagas disease infection. These data suggest a need to strengthen epidemiological surveillance and integrate appropriate control actions targeting triatomines, T. cruzi reservoirs, and human populations. Our data also identify Chagas disease

  12. Tolerance and safety of nifurtimox in patients with chronic chagas disease.

    Science.gov (United States)

    Jackson, Yves; Alirol, Emilie; Getaz, Laurent; Wolff, Hans; Combescure, Christophe; Chappuis, François

    2010-11-15

    Nifurtimox has been used to treat Chagas disease for 40 years, but tolerance and safety data in adults are scarce. We aimed to evaluate nifurtimox tolerance and safety in a cohort of Trypanosoma cruzi-infected adult patients in a country of nonendemicity. This observational study included all consecutive adults patients who were given a diagnosis of T. cruzi infection from June through December 2008. Eligible patients received nifurtimox at 10 mg/kg/day for 60 days, with regular medical and biological follow-up. Adverse events (AEs) were recorded according to Common Terminology Criteria for Adverse Events, version 3.0. Eighty-one patients received nifurtimox. Eight were lost to follow-up during treatment, and 41 (56.2%) completed the 60-day course. All premature treatment terminations were caused by AEs; 97.5% of patients suffered from AEs, mostly expected (90.5%) and not severe. Gastrointestinal symptoms predominated. Six (7.4%) patients presented with a suspected unexpected serious adverse reaction: drug reaction with eosinophilia and systemic symptoms (n = 3), Quincke edema (n = 1), acute myocarditis (n = 1), and anaphylaxis (n = 1). Patients with 3 or more AEs had an increased risk of premature treatment termination (hazard ratio, 8.42; 95% confidence interval, 1.6-45.5). Nifurtimox is poorly tolerated among adults with chronic Chagas disease, resulting in a low treatment completion rate. Considering the significant risk of serious AEs, close monitoring is required, which may be difficult to implement in poor rural areas of countries of endemicity. The safety and efficacy of nifurtimox and benznidazole should be compared to improve current therapeutic recommendations, and pharmacovigilance systems should be enhanced.

  13. Diet regulates liver autophagy differentially in murine acute Trypanosoma cruzi infection.

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    Lizardo, Kezia; Almonte, Vanessa; Law, Calvin; Aiyyappan, Janeesh Plakkal; Cui, Min-Hui; Nagajyothi, Jyothi F

    2017-02-01

    Chagas disease is a tropical parasitic disease caused by the protozoan Trypanosoma cruzi, which affects about ten million people in its endemic regions of Latin America. After the initial acute stage of infection, 60-80% of infected individuals remain asymptomatic for several years to a lifetime; however, the rest develop the debilitating symptomatic stage, which affects the nervous system, digestive system, and heart. The challenges of Chagas disease have become global due to immigration. Despite well-documented dietary changes accompanying immigration, as well as a transition to a western style diet in the Chagas endemic regions, the role of host metabolism in the pathogenesis of Chagas disease remains underexplored. We have previously used a mouse model to show that host diet is a key factor regulating cardiomyopathy in Chagas disease. In this study, we investigated the effect of a high-fat diet on liver morphology and physiology, lipid metabolism, immune signaling, energy homeostasis, and stress responses in the murine model of acute T. cruzi infection. Our results indicate that in T. cruzi-infected mice, diet differentially regulates several liver processes, including autophagy, a stress response mechanism, with corresponding implications for human Chagas disease patients.

  14. Chagas Disease, Migration and Community Settlement Patterns in Arequipa, Peru

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    Gilman, Robert H.; Cornejo del Carpio, Juan G.; Naquira, Cesar; Bern, Caryn; Levy, Michael Z.

    2009-01-01

    Background Chagas disease is one of the most important neglected tropical diseases in the Americas. Vectorborne transmission of Chagas disease has been historically rare in urban settings. However, in marginal communities near the city of Arequipa, Peru, urban transmission cycles have become established. We examined the history of migration and settlement patterns in these communities, and their connections to Chagas disease transmission. Methodology/Principal Findings This was a qualitative study that employed focus group discussions and in-depth interviews. Five focus groups and 50 in-depth interviews were carried out with 94 community members from three shantytowns and two traditional towns near Arequipa, Peru. Focus groups utilized participatory methodologies to explore the community's mobility patterns and the historical and current presence of triatomine vectors. In-depth interviews based on event history calendars explored participants' migration patterns and experience with Chagas disease and vectors. Focus group data were analyzed using participatory analysis methodologies, and interview data were coded and analyzed using a grounded theory approach. Entomologic data were provided by an ongoing vector control campaign. We found that migrants to shantytowns in Arequipa were unlikely to have brought triatomines to the city upon arrival. Frequent seasonal moves, however, took shantytown residents to valleys surrounding Arequipa where vectors are prevalent. In addition, the pattern of settlement of shantytowns and the practice of raising domestic animals by residents creates a favorable environment for vector proliferation and dispersal. Finally, we uncovered a phenomenon of population loss and replacement by low-income migrants in one traditional town, which created the human settlement pattern of a new shantytown within this traditional community. Conclusions/Significance The pattern of human migration is therefore an important underlying determinant of

  15. Citral: a monoterpene with prophylactic and therapeutic anti-nociceptive effects in experimental models of acute and chronic pain.

    Science.gov (United States)

    Nishijima, Catarine M; Ganev, Ellen G; Mazzardo-Martins, Leidiane; Martins, Daniel F; Rocha, Lúcia R M; Santos, Adair R S; Hiruma-Lima, Clelia A

    2014-08-05

    Citral (3,7-dimethyl-2,6-octadienal) is an open-chain monoterpenoid present in the essential oils of several medicinal plants. The aim of this work was to evaluate the effects of orally administered citral in experimental models of acute and chronic nociception, inflammation, and gastric ulcers caused by non-steroidal anti-inflammatory drugs (NSAIDs). Oral treatment with citral significantly inhibited the neurogenic and inflammatory pain responses induced by intra-plantar injection of formalin. Citral also had prophylactic and therapeutic anti-nociceptive effects against mechanical hyperalgesia in plantar incision surgery, chronic regional pain syndrome, and partial ligation of sciatic nerve models, without producing any significant motor dysfunction. In addition, citral markedly attenuated the pain response induced by intra-plantar injection of glutamate and phorbol 12-myristate 13-acetate (PMA, a protein kinase C activator), as well as by intrathecal (i.t.) injection of ionotropic and metabotropic glutamate receptor agonists (N-methyl-D-aspartic acid [NMDA] and 1-amino-1,3-dicarboxycyclopentane [trans-ACPD], respectively), substance P, and cytokine tumour necrosis factor-α. However, citral potentiated behaviours indicative of pain caused by i.t., but not intra-plantar, injection of a transient receptor potential vanilloid receptor type 1 (TRPV1) agonist. Finally, the anti-nociceptive action of citral was found to involve significant activation of the 5-HT2A serotonin receptor. The effect of citral was accompanied by a gastro-protective effect against NSAID-induced ulcers. Together, these results show the potential of citral as a new drug for the treatment of pain. Copyright © 2014 Elsevier B.V. All rights reserved.

  16. The Impact of Different Plasma Glucose Levels on Heart Rate in Experimental Rats With Acute Myocardial Infarction.

    Science.gov (United States)

    Pan, Guo-Zhong; Xie, Jing; Tian, Xiao-Fang; Yang, Shi-Wei; Zhou, Yu-Jie

    2016-08-01

    The aim of the study was to evaluate the impact of different plasma glucose levels on heart rate (HR) in experimental rats with acute myocardial infarction (AMI). One hundred and twenty-one male Wistar rats were randomly divided into AMI group (n = 70) and sham-operation group (n = 51). Both groups had low, normal and high glucose levels, respectively. In the former group, hypertonic glucose was injected into the rats to make their blood glucose levels above 16 mmol/L and insulin below 3.3 mmol/L; then, the left anterior descending artery was ligated. In the later group, the models of different blood glucose levels were the same as the former ones, but false operations, thread without ligating, were given to the rats. Electrocardiogram and troponin I (TnI) confirmed that the models were prepared successfully. Electrocardiogram expression of AMI was the formation of Q-wave in over three adjacent leads and abnormal elevation of TnI. The HR of the rats in the hypoglycemic group is higher than that of the hyperglycemic group and normal blood glucose group before AMI (P < 0.05). The HR of the hyperglycemic rats is higher than that of the hypoglycemic group and normal blood glucose group after AMI (P < 0.05). In the hypoglycemic group, the HR of the rats who suffered from AMI was lower than that of the rats of the sham group (P < 0.05). Hypoglycemia allows faster HR and the HR in the rats with hyperglycemia is higher than that in the rats with hypoglycemia among the AMI rats.

  17. Changes in Coronary Blood Flow After Acute Myocardial Infarction: Insights From a Patient Study and an Experimental Porcine Model.

    Science.gov (United States)

    de Waard, Guus A; Hollander, Maurits R; Teunissen, Paul F A; Jansen, Matthijs F; Eerenberg, Elise S; Beek, Aernout M; Marques, Koen M; van de Ven, Peter M; Garrelds, Ingrid M; Danser, A H Jan; Duncker, Dirk J; van Royen, Niels

    2016-03-28

    The aim of this study was to determine the effects of an acute myocardial infarction (AMI) on baseline and hyperemic flow in both culprit and nonculprit arteries. An impaired coronary flow reserve (CFR) after AMI is related to worse outcomes. The individual contribution of resting and hyperemic flow to the reduction of CFR is unknown. Furthermore, it is unclear whether currently used experimental models of AMI resemble the clinical situation with respect to coronary flow parameters. Intracoronary Doppler flow velocity measurements were obtained in culprit and nonculprit arteries immediately after successfully revascularized ST-segment elevation myocardial infarction (n = 40). Stable patients without obstructive coronary artery disease served as control subjects and were selected by propensity-score matching (n = 40). Similar measurements in an AMI porcine model were taken both before and immediately after 75-min balloon occlusion of the left circumflex artery (n = 11). In the culprit artery, CFR was 36% lower than in matched control subjects (Δ = -0.9; 1.8 ± 0.9 vs. 2.8 ± 0.7; p infarct size as a percentage of the left ventricle in both patients (r = -0.48; p = 0.001) and swine (r = -0.61; p = 0.047). CFR in both culprit and nonculprit coronary arteries decreases after AMI with contributions from both an increased baseline flow and a decreased hyperemic flow. The decreased CFR after AMI in culprit and nonculprit vessels is not a result of pre-existing microvascular dysfunction, but represents a combination of post-occlusive hyperemia, myocardial necrosis, hemorrhagic microvascular injury, compensatory hyperkinesis, and neurohumoral vasoconstriction. Copyright © 2016 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

  18. EVALUATION OF DIPYRIDAMOLE ON ACUTE AND SUBACUTE MODELS OF INFLAMMATION IN MALE WISTAR RATS: AN EXPERIMENTAL STUDY

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    Angadi Netravathi B, Hiremath Shrishail V , Suranagi Vijayalakshmi V.

    2015-07-01

    Full Text Available Background: Atherosclerosis and its complications remains the major cause of death and premature disability. Atherogenesis involves elements of inflammation, a process that now provides a unifying theme in the pathogenesis of the disease. Anti-platelet drugs are currently used in the treatment of atherosclerosis and its complications. Our study evaluated the influence of dipyridamole on acute and sub-acute models of inflammation in male Wistar rats. Methods: Male Wistar rats (150-200g were divided into three groups i.e. control, Aspirin and dipyridamole (n=6 animals in each group. The effect of dipyridamole, administered orally, on inflammation was studied using acute (carrageenan induced rat paw edema and sub-acute (cotton pellet granuloma and histopathological examination of grass piths models. Experiment was conducted according to the Committee for the Purpose of Control and Supervision on Experiments on Animals (CPCSEA guidelines. Analysis was done using one way ANOVA followed by Post Hoc Test of Dunnets. P<0.05 was considered as statistically significant. Results: Dipyridamole showed significant inhibition of rat paw edema in acute model (P<0.01 and granuloma dry weight, in sub acute model of inflammation when compared to control (P<0.01. Histopathological examination of grass pith revealed markedly reduced fibroblasts, granulation tissue, fibrous tissue and collagen in dipyridamole group when compared to control. Conclusion: Dipyridamole exhibited a significant anti inflammatory activity in acute and sub-acute models of inflammation.

  19. Experimental pancreatitis in the rat: role of bile reflux in sodium taurocholate-induced acute haemorrhagic pancreatitis

    NARCIS (Netherlands)

    Lange, J. F.; van Gool, J.; Tytgat, G. N.

    1986-01-01

    Mortality of sodium taurocholate-induced acute haemorrhagic pancreatitis in the rat was prevented by biliary diversion. Bile reflux into the pancreas after the induction of pancreatitis is postulated to be a major factor affecting mortality of this popular model of acute pancreatitis. The reduction

  20. Low-methoxyl lemon pectin attenuates inflammatory responses and improves intestinal barrier integrity in caerulein-induced experimental acute pancreatitis

    NARCIS (Netherlands)

    Sun, Yajun; He, Yue; Wang, Fei; Zhang, Hao; de Vos, Paul; Sun, Jia

    Scope: Acute pancreatitis (AP) is a common clinical acute abdominal disease. The intestinal injury associated with AP will aggravate the condition retroactively. This study investigates whether the low-methoxyl pectin (LMP) isolated from lemon could attenuate AP and associated intestinal injury.

  1. Mesenchymal bone marrow cell therapy in a mouse model of chagas disease. Where do the cells go?

    Directory of Open Access Journals (Sweden)

    Jasmin

    Full Text Available Chagas disease, resulting from infection with the parasite Trypanosoma cruzi (T. cruzi, is a major cause of cardiomyopathy in Latin America. Drug therapy for acute and chronic disease is limited. Stem cell therapy with bone marrow mesenchymal cells (MSCs has emerged as a novel therapeutic option for cell death-related heart diseases, but efficacy of MSC has not been tested in Chagas disease.We now report the use of cell-tracking strategies with nanoparticle labeled MSC to investigate migration of transplanted MSC in a murine model of Chagas disease, and correlate MSC biodistribution with glucose metabolism and morphology of heart in chagasic mice by small animal positron emission tomography (microPET. Mice were infected intraperitoneally with trypomastigotes of the Brazil strain of T. cruzi and treated by tail vein injection with MSC one month after infection. MSCs were labeled with near infrared fluorescent nanoparticles and tracked by an in vivo imaging system (IVIS. Our IVIS results two days after transplant revealed that a small, but significant, number of cells migrated to chagasic hearts when compared with control animals, whereas the vast majority of labeled MSC migrated to liver, lungs and spleen. Additionally, the microPET technique demonstrated that therapy with MSC reduced right ventricular dilation, a phenotype of the chagasic mouse model.We conclude that the beneficial effects of MSC therapy in chagasic mice arise from an indirect action of the cells in the heart rather than a direct action due to incorporation of large numbers of transplanted MSC into working myocardium.

  2. A case of megacolon in Rio Grande Valley as a possible case of Chagas disease

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    Karl Reinhard

    2003-01-01

    Full Text Available We have been searching for evidence of Chagas disease in mummified human remains. Specifically, we have looked for evidence of alteration of intestinal or fecal morphology consistent with megacolon, a condition associated with Chagas disease. One prehistoric individual recovered from the Chihuahuan Desert near the Rio Grande exhibits such pathology. We present documentation of this case. We are certain that this individual presents a profoundly altered large intestinal tract and we suggest that further research should focus on confirmation of a diagnosis of Chagas disease. We propose that the prehistoric activity and dietary patterns in Chihuahua Desert hunter/gatherers promoted the pathoecology of Chagas disease.

  3. Physician Knowledge of Chagas Disease in Hispanic Immigrants Living in Appalachian Ohio.

    Science.gov (United States)

    Amstutz-Szalay, Shelley

    2017-06-01

    Studies have indicated that US physicians may not consider Chagas disease when diagnosing immigrant patients from Chagas-endemic areas. The purpose of this study was to evaluate physician knowledge of Chagas disease in six Appalachian Ohio counties. Physician knowledge was assessed by self-administrated survey (n = 105). Over 80 % of physicians reported that their current knowledge of Chagas disease was limited or very limited, and 50 % reported never considering Chagas disease diagnosis for their at-risk patients. Nearly 70 % of physicians were unaware of the percentage of chronic Chagas patients that develop clinical disease, and 36 % could not correctly identify the disease course. In addition, over 30 % of physicians reported that no services were available within their practice to assist Spanish-speaking patients with limited English proficiency. A lack of physician awareness of Chagas disease, coupled with a lack of translation services, may create a barrier to care by decreasing the likelihood of identification of patients at risk for Chagas disease. The results of this study support the need for interventions to ensure proper diagnosis and treatment of Chagas disease in Hispanic immigrants in rural Appalachian Ohio.

  4. Present situation and new strategies for Chagas disease chemotherapy: a proposal

    Directory of Open Access Journals (Sweden)

    José Rodrigues Coura

    2009-07-01

    Full Text Available Treatments for Chagas disease have been administered since the first attempts by Mayer & Rocha Lima (1912, 1914 and up to the drugs currently in use (nifurtimox and benznidazole, along with potential drugs such as allopurinol and first, second and third-generation antifungal agents (imidazoles and triazoles, in separate form. Several diseases such as tuberculosis, leprosy and AIDS only came under control after they were treated with associations of drugs with different mechanisms of action. This not only boosts the action of the different compounds, but also may avoid the development of parasite resistance .To this end, over the short term, we propose experimental studies on laboratory animals and clinical trials with the following associations: (i nifurtimox (8 mg/kg/day + benznidazole (5 mg/kg/day x 60 consecutive days; (ii nifurtimox (8 mg/kg/day or benznidazole (5 mg/kg/day + allopurinol (8-10 mg/kg/day x 60 days and (iii nifurtimox (8 mg/kg/day or benznidazole (5 mg/kg/day + ketoconazole, fluconazole or itraconazole (5-6 mg/kg/day x 60 consecutive days. The doses of the drugs and the treatment schedules for the clinical trials must be adapted according to the side effects. From these, other double or triple associations could be made, using drugs with different mechanisms of action. This proposal does not exclude investigations on new drugs over the median and long terms, targeting other aspects of the metabolism of Trypanosoma cruzi. Until such time as the ideal drug for specific treatment of Chagas disease might be discovered, we need to develop new strategies for achieving greater efficacy with the old drugs in associations and to develop rational experimentation with new drugs.

  5. Cecílio Romaña, o sinal de Romaña e a doença de Chagas

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    João Carlos Pinto Dias

    1997-10-01

    Full Text Available Recentemente falecido em Barcelona, Cecílio Romaña foi um importante tropicologista argentino com muitas contribuições à clínica, ao controle e à patologia da doença de Chagas entre 1930 e 1960. Em 1935, Romaña tornou-se famoso por sua precisa descrição do complexo oftalmo-ganglionar, o mais típico dos sinais de porta de entrada da doença de Chagas humana, sinal este que logo ficou conhecido em toda a América Latina com o nome de "sinal de Romaña", por proposição de dois pesquisadores brasileiros, Emmanuel Dias e Evandro Chagas. O achado de Romaña causou enorme polêmica com o grande Salvador Mazza, que não reconheceu a especificidade do sinal e, muito menos, aceitou a proposta nomenclatura. Estes fatos são relatados no presente artigo, que homenageia Cecílio Romaña e destaca o enorme impacto de sua descoberta para o conhecimento da doença de Chagas aguda em toda sua área endêmica.Cecílio Romaña was an important Argentinean researcher dedicated to tropical diseases in the period 1930-1960, recently died in Barcelona. Working mainly on the epidemiological, clinical and pathological aspects of American trypanosomiasis, Romaña became very famous in 1935 when he accurately described the most typical portal recognized in all the endemic area with the cognomen of "Romaña sign". This description caused an enormous polemic with Romaña's then director, the great Salvador Mazza, who never accepted the specificity of the sign and, much less, its popular name (which was proposed by the Brazilian researchers Emmanuel Dias and Evandro Chagas. This history is briefly summarized in the present article, as well as the great impact of Romaña's discovery in the recognition of the acute Chagas' disease in all the endemic area.

  6. Assessment and epidemiology of Chagas' disease in patients treated in Araguaina - Tocantins; Avaliacao e epidemiologia da cardiopatia chagasica em pacientes atendidos em Araguaina - Tocantins

    Energy Technology Data Exchange (ETDEWEB)

    Correa, Valeria Rita

    2010-07-01

    Chagas disease (AD) was described by Carlos Chagas in 1909. It is caused by a parasite T. cruzi, transmitted by bugs, by blood transfusion, vertical and orally. The DC has two phases: acute and chronic. The evolution to the cardiac form occurs in about 30% of chronic cases and is the largest cause of mortality in chronic Chagas disease. The aim of this study was to Chagas' disease in patients of Tocantins, compared with other heart patients and asymptomatic from the standpoint of non-invasive exams using radiant energies such as echocardiography and ECG and RX. The descriptive study included 80 patients, 20 chronic form of Chagas disease, 20 indeterminate, 20 with other heart diseases, and 20 controls. There was a prevalence of 9.5% of chagasic patients treated in outpatient cardiology at Araguaina Tocantins, and 7.3% in chronic and 2.21% in the indeterminate. Of the chronic patients in the study 50% had mega esophagus and megacolon 4 (20%). Most patients had no family history of AD, nor was a smoker or drinker. Major electrocardiographic abnormalities found refer to driving. The evaluation of ICT, the chronic chagasic showed that increased by 40% of patients, 40% had esophageal changes and 20% of patients had megacolon s. The echocardiogram was abnormal in 42%). 27% of patients had EF below 55% changed. Changes in segmental contractility and Asynchrony septum were found in 80% of chronic Chagas disease. In 80% of the patients was observed diastolic dysfunction. The valvular changes occurred in 75%. Electrocardiographic abnormalities occurred in 80% of patients with CCC, while the other heart had ECG changes. Arterial hypertension had an incidence of 45% in patients with CCC and 40% in FCI. The systolic and diastolic ventricular dysfunction was more prevalent in groups that had an abnormal ECG and arrhythmia. Observed that the group of chagasic decreased ejection fraction is correlated to a higher incidence of arrhythmias besides diastolic dysfunction and

  7. Experimental Ehrlichia canis infection changes acute-phase proteins A infecção experimental por Ehrlichia canis altera as proteínas de fase aguda

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    Thiago Demarchi Munhoz

    2012-09-01

    Full Text Available Early diagnosis of canine ehrlichiosis favors prompt institution of treatment and improves the prognosis for the animal, since this disease causes mortality among dogs. Studies have shown that determining the concentration of acute-phase proteins (APPs may contribute towards early detection of disease and aid in predicting the prognosis. This study aimed to evaluate the APP profile in dogs experimentally infected with Ehrlichia canis, at the start of the infection and after treatment. It also investigated whether any correlation between APP levels and the clinical and laboratory alterations over the course of the disease would be possible. The results obtained showed abnormal levels of all the APPs on the third day after infection (D3, with the highest levels being reached on D18, with the exception of ceruloplasmin and acid glycoprotein, which presented their peaks on D6 and D12 respectively. We concluded that assessment of APP levels could contribute towards establishing an early diagnosis of canine ehrlichiosis, particularly regarding acid glycoprotein and ceruloplasmin, since these proteins were detected at increased levels even before the onset of clinical and laboratory findings of the disease.O diagnóstico precoce da erliquiose canina favorece a pronta instituição do tratamento e melhora o prognóstico do animal, pois se trata de uma doença de alta mortalidade em cães. Estudos têm apontado que a determinação da concentração de proteínas de fase aguda (PFA pode contribuir para detecção precoce de doenças e auxiliar na predição do prognóstico. O presente estudo objetivou avaliar o perfil de proteínas de fase aguda (PFA em cães experimentalmente infectados com Ehrlichia canis, no início da infecção e após o tratamento. Além disso, se seria possível associá-las com as alterações clínico-laboratoriais durante o curso da doença. Os resultados obtidos evidenciaram que todas as PFA estudadas alteraram suas concentra

  8. Interactive Media on Chagas Disease: Development and Content

    Directory of Open Access Journals (Sweden)

    Claudinei Caetano de Souza

    2013-10-01

    Full Text Available An interactive media on Chagas disease was developed as an educational tool, on the context of the scientific research and dissemination actions of the National Institute of Structural Biotechnology and Medicinal Chemistry in Infectious Diseases (INBEQMeDI. Different computational resources were used either in terms of hardware and software. The media contains 13 videos that range from 30 seconds to 4 minutes, all with information about Chagas disease, showing the social and economic aspects; the research made by the INBEQMeDI group; different aspects of the disease illustrated by slides arranged in a mobile carousel, and radio programs, with funny skits. The target audience for use of this feature is students aged 10 to 17 years. Teachers of areas of science and biology, through a partnership with the Agency of Education of the State of São Paulo, will be invited to plan a strategy for media use with their students.

  9. Current situation of Chagas disease in Central America

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    Carlos Ponce

    2007-10-01

    Full Text Available Chagas disease in Central America is known since 1913 when the first human case was reported in El Salvador. The other Central American countries reported their first cases between 1933 and 1967. On October 1997 was launched the Central American Initiative for Chagas Disease Control (IPCA. The objectives of this sub-regional Initiative are: (1 the elimination of Rhodnius prolixus in Central America; (2 the reduction of the domiciliary infestation of Triatoma dimidiata; and (3 the elimination of the transfusion transmission of Trypanosoma cruzi. Significant advancements being close to the elimination of R. prolixus in Central America and the control of the transfusion transmission has been a transcendent achievement for the sub-region. The main challenges that the IPCA will have in the close future are: developing effective strategies for control and surveillance of T. dimidiata; and surveillance of other emerging triatominae species like R. pallescens, T. nitida, and T. ryckmani.

  10. Increased osmotic sensitivity for antidiuretic response in chronic chagas' disease

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    Joel Paulo Russomano Veiga

    1985-06-01

    Full Text Available The osmotic threshold for attaining the antidiuretic response to hypertonic saline infusion and Progressive dehydration was studied in 31 patients with the chronic form of Chagas' disease and 16 control patients. The chagasic patients exhibited enhanced osmoticsensitivity to the antidiuretic response. This was demonstrated by lower values of the increments in plasma osmolarity sufficient to induce a significant fall in water clearance, without alterations in the osmolar clearance or creatinine excretion. The time needed to attain the antidiuretic response was shorterfor chagasics in relation to normal subjects. The results suggest the existence of a disturbance in the fine control of osmoregulation in the chagasic patients. They are interpreted to be a consequence of the denervation in hypothalamic or extrahypothalamic areas that regulate the secretion of vasopressin in chronic Chagas' disease.

  11. [Efficacy of nifurtimox for the treatment of chronic Chagas disease].

    Science.gov (United States)

    Fuentes B, Rodrigo; Maturana A, Mario; de la Cruz M, Rolando

    2012-02-01

    Most Chagas patients belong to the chronic indeterminate stage, in which pharmacological treatment has an inconclusive outcome. To evaluate the efficacy of nifurtimox treatment in chronic asymptomatic Trypanosoma cruzi infection. We performed a systematic review and meta-analysis of electronically published literature, with no language, type of study, age or gender restrictions, until September 2010. Studies of chronic asymptomatic Chagas disease patients treated exclusively with nifurtimox were included in the analysis. Treatment efficacy was evaluated using parasitological or serological parameters. Of 463 identified studies, 7 were finally selected: 6 observational studies and 1 randomized clinical trial; 4 of the studies were in adults, 3 in children nifurtimox in this clinical phase of T. cruzi infection.

  12. Therapy of Chagas Disease: Implications for Levels of Prevention

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    Sergio Sosa-Estani

    2012-01-01

    Full Text Available This paper reviews the evidence supporting the use of etiological treatment for Chagas disease that has changed the standard of care for patients with Trypanosoma cruzi infection in the last decades. Implications of this evidence on different levels of prevention as well as gaps in current knowledge are also discussed. In this regard, etiological treatment has shown to be beneficial as an intervention for secondary prevention to successfully cure the infection or to delay, reduce, or prevent the progression to disease, and as primary disease prevention by breaking the chain of transmission. Timely diagnosis during initial stages would allow for the prescription of appropriate therapies mainly in the primary health care system thus improving chances for a better quality of life. Based on current evidence, etiological treatment has to be considered as an essential public health strategy useful to reduce disease burden and to eliminate Chagas disease altogether.

  13. Neglected Parasitic Infections in the United States: Chagas Disease

    Science.gov (United States)

    Montgomery, Susan P.; Starr, Michelle C.; Cantey, Paul T.; Edwards, Morven S.; Meymandi, Sheba K.

    2014-01-01

    Chagas disease, which is caused by the protozoan parasite Trypanosoma cruzi, can lead to severe cardiac and gastrointestinal disease. Most persons acquire this infection through contact with vector bugs carrying T. cruzi in endemic areas of Latin America. Infection can also be acquired by congenital, transfusion, transplantation, and foodborne transmission. Although an estimated 300,000 persons with Chagas disease live in the United States, little is known about the burden of chagasic heart disease. It is not known how often congenital or vector-borne transmission of T. cruzi occurs in the United States, although it is known that infected mothers and infected vector bugs are found in this country. Better diagnostic tests and treatment drugs are needed to improve patient care, and research is needed to define transmission risks and develop strategies to prevent new infections and reduce the burden of disease. PMID:24808250

  14. Estado actual en el tratamiento de la enfermedad de Chagas

    OpenAIRE

    Apt B,Werner; ZULANTAY A,INÉS

    2011-01-01

    Efficient drugs against Chagas' disease must have an effect on the amastigote forms or intracellular reproduction elements of Trypanosoma cruzi (T. cruzi). Trypomastigote and epimastigote forms derive from the former and their response to medications is less marked. The only drugs used in humans are nifurtimox (NF) and benznidazole (BNZ). Other useful medications are allopurinol and itraconazole. NF acts producing free radicals and BNZ inhibits the synthesis of macromolecules. There is consen...

  15. Chagas Disease in Dogs from Endemic Areas of Costa Rica

    OpenAIRE

    Montenegro Victor M; Jiménez Maurico; Dias JC Pinto; Zeledón Rodrigo

    2002-01-01

    Dogs with the presumptive diagnosis of Chagas disease are commonly sent to our School of Veterinary Medicine by independent veterinarians. This prompted us to evaluate the prevalence of canine trypanosomiasis in some villages of the Central Valley of Costa Rica. A total of 54 dogs (21 males and 33 females) from five rural villages, with ages between 3 months and 10 years old, were bled and submitted to three serological tests: indirect immunofluorescence, indirect hemagglutination and ELISA. ...

  16. Epicuticular lipids induce aggregation in Chagas disease vectors

    OpenAIRE

    Juárez M Patricia; Mijailovsky Sergio J; Girotti Juan R; Figueiras Alicia

    2009-01-01

    Abstract Background The triatomine bugs are vectors of the protozoan parasite Trypanosoma cruzi, the causative agent of Chagas disease. Aggregation behavior plays an important role in their survival by facilitating the location of refuges and cohesion of aggregates, helping to keep them safely assembled into shelters during daylight time, when they are vulnerable to predators. There are evidences that aggregation is mediated by thigmotaxis, by volatile cues from their faeces, and by hexane-ex...

  17. Economic evaluation of Chagas disease screening in Spain.

    Science.gov (United States)

    Imaz-Iglesia, Iñaki; Miguel, Lucía García-San; Ayala-Morillas, L Eduardo; García-Pérez, Lidia; González-Enríquez, Jesús; Blasco-Hernández, Teresa; Martín-Águeda, María Belén; Sarría-Santamera, Antonio

    2015-08-01

    Although Spain is the European country with the highest Chagas disease burden, the country does not have a national control program of the disease. The purpose of this study is to evaluate the efficiency of several strategies for Chagas disease screening among Latin American residents living in Spain. The following screening strategies were evaluated: (1) non-screening; (2) screening of the Latin American pregnant women and their newborns; (3) screening also the relatives of the positive pregnant women; (4) screening also the relatives of the negative pregnant women. A cost-utility analysis was carried out to compare the four strategies from two perspectives, the societal and the Spanish National Health System (SNHS). A decision tree representing the clinical evolution of Chagas disease throughout patient's life was built. The strategies were compared through the incremental cost-utility ratio, using euros as cost measurement and quality-adjusted life years as utility measurement. A sensitivity analysis was performed to test the model parameters and their influence on the results. We found the "Non-screening" as the most expensive and less effective of the evaluated strategies, from both the societal and the SNHS perspectives. Among the screening evaluated strategies the most efficient was, from both perspectives, to extent the antenatal screening of the Latin American pregnant women and their newborns up to the relatives of the positive women. Several parameters influenced significantly on the sensitivity analyses, particularly the chronic treatment efficacy or the prevalence of Chagas disease. In conclusion, for the general Latin American immigrants living in Spain the most efficient would be to screen the Latin American mothers, their newborns and the close relatives of the mothers with a positive serology. However for higher prevalence immigrant population the most efficient intervention would be to extend the program to the close relatives of the negative

  18. Current situation and perspectives regarding human Chagas disease in midwestern of the state of Minas Gerais, Brazil

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    Christiane Santos Matos

    2014-06-01

    Full Text Available Recognising the importance of Chagas disease in Brazil, Bambuí set up epidemiological surveillance for Chagas disease in 1974 and was the first municipality to do so. To ascertain the current epidemiology of Chagas disease in this municipality, 1.782 blood samples from the general population were analysed; 7.7% of samples were found to be seropositive for Chagas disease. A strong positive correlation between increasing age and Chagas disease was evident in both genders, with the highest prevalence in individuals aged over 60 years. Clinically, the cardiodigestive form of Chagas disease was the most common in these samples. These data confirm the interruption of Trypanosoma cruzi transmission, in parallel with a still important residual morbidity of Chagas disease in the county, thus supporting political decisions that will prioritise epidemiological surveillance and medical treatment of Chagas disease in the coming years.

  19. Different Therapeutic Outcomes of Benznidazole and VNI Treatments in Different Genders in Mouse Experimental Models of Trypanosoma cruzi Infection

    National Research Council Canada - National Science Library

    Guedes-da-Silva, F H; Batista, D G J; da Silva, C F; Meuser, M B; Simões-Silva, M R; de Araújo, J S; Ferreira, C G; Moreira, O C; Britto, C; Lepesheva, G I; Soeiro, Maria de Nazaré C

    2015-01-01

    ...) and with the potent experimental T. cruzi CYP51 inhibitor VNI in mouse models of Chagas disease by using different animal genders and parasite strains and employing distinct types of therapeutic schemes...

  20. A Paratransgenic Strategy for the Control of Chagas Disease

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    Ivy Hurwitz

    2012-01-01

    Full Text Available Chagas disease results from infection with the parasite Trypanosoma cruzi. This disease remains a significant cause of morbidity and mortality in central and south America. Chagas disease now exists and is detected worldwide because of human migration. Control of Chagas disease has relied mainly on vector eradication however, the development of insect resistance to pesticides, coupled with cost and adverse health effects of insecticide treatments, has prompted our group to investigate novel methods of transmission control. Our laboratory has been instrumental in the development of the paratransgenic strategy to control vectorial transmission of T. cruzi. In this paper, we discuss various components of the paratransgenic approach. Specifically, we describe classes of molecules that can serve as effectors, including antimicrobial peptides, endoglucanases, and highly specific single chain antibodies that target surface glycoprotein tags on the surface of T. cruzi. Furthermore, we address evolving concepts related to field dispersal of engineered bacteria as part of the paratransgenic control strategy and attendant risk assessment evaluation.

  1. The Role of Haptoglobin Genotypes in Chagas Disease

    Science.gov (United States)

    Mundaray Fernández, Ninomar; Fernández-Mestre, Mercedes

    2014-01-01

    Although the number of people infected with T. cruzi is on the rise, host genetic and immune components that are crucial in the development of the Chagas disease have been discovered. We investigated the frequency of polymorphisms in the gene encoding haptoglobin of patients with chronic Chagas disease. The results suggest that while the HP1-1 genotype may confer protection against infection and the development of chronic Chagas disease due to the rapid metabolism of the Hp1-1-Hb complex and its anti-inflammatory activity, the presence of HP2-2 genotype may increase susceptibility towards a chronic condition of the disease due to a slow metabolism of the Hp2-2-Hb complex, lower antioxidant activity, and increased inflammatory reactivity, which lead to cell damage and a deterioration of the cardiac function. Finally, correlations between HP genotypes in different age groups and cardiac manifestations suggest that HP polymorphism could influence the prognosis of this infectious disease. This study shows some of the relevant aspects of the haptoglobin gene polymorphism and its implications in the T. cruzi infection. PMID:25147423

  2. Seroprevalence of Chagas infection in the donor population.

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    Ben A Zaniello

    Full Text Available We retrospectively calculated the prevalence and epidemiologic characteristics of Chagas infection in the New York blood donor population over three years utilizing the New York Blood Center's database of the New York metropolitan area donor population. Seventy Trypanosoma cruzi positive donors were identified from among 876,614 donors over a 3-year period, giving an adjusted prevalence of 0.0083%, with 0.0080% in 2007, 0.0073% in 2008, and 0.0097% in 2009. When filtered only for self-described "Hispanic/Latino" donors, there were 52 Chagas positive donors in that 3-year period (among 105,122 self-described Hispanic donors with an adjusted prevalence of 0.052%, with 0.055% in 2007, 0.047% in 2008, and 0.053% in 2009. In conclusion, we found a persistent population of patients with Chagas infection in the New York metropolitan area donor population. There was geographic localization of cases which aligned with Latin American immigration clusters.

  3. Trypanosoma cruzi and Chagas' Disease in the United States

    Science.gov (United States)

    Bern, Caryn; Kjos, Sonia; Yabsley, Michael J.; Montgomery, Susan P.

    2011-01-01

    Summary: Chagas' disease is caused by the protozoan parasite Trypanosoma cruzi and causes potentially life-threatening disease of the heart and gastrointestinal tract. The southern half of the United States contains enzootic cycles of T. cruzi, involving 11 recognized triatomine vector species. The greatest vector diversity and density occur in the western United States, where woodrats are the most common reservoir; other rodents, raccoons, skunks, and coyotes are also infected with T. cruzi. In the eastern United States, the prevalence of T. cruzi is highest in raccoons, opossums, armadillos, and skunks. A total of 7 autochthonous vector-borne human infections have been reported in Texas, California, Tennessee, and Louisiana; many others are thought to go unrecognized. Nevertheless, most T. cruzi-infected individuals in the United States are immigrants from areas of endemicity in Latin America. Seven transfusion-associated and 6 organ donor-derived T. cruzi infections have been documented in the United States and Canada. As improved control of vector- and blood-borne T. cruzi transmission decreases the burden in countries where the disease is historically endemic and imported Chagas' disease is increasingly recognized outside Latin America, the United States can play an important role in addressing the altered epidemiology of Chagas' disease in the 21st century. PMID:21976603

  4. The Role of Haptoglobin Genotypes in Chagas Disease

    Directory of Open Access Journals (Sweden)

    Ninomar Mundaray Fernández

    2014-01-01

    Full Text Available Although the number of people infected with T. cruzi is on the rise, host genetic and immune components that are crucial in the development of the Chagas disease have been discovered. We investigated the frequency of polymorphisms in the gene encoding haptoglobin of patients with chronic Chagas disease. The results suggest that while the HP1-1 genotype may confer protection against infection and the development of chronic Chagas disease due to the rapid metabolism of the Hp1-1-Hb complex and its anti-inflammatory activity, the presence of HP2-2 genotype may increase susceptibility towards a chronic condition of the disease due to a slow metabolism of the Hp2-2-Hb complex, lower antioxidant activity, and increased inflammatory reactivity, which lead to cell damage and a deterioration of the cardiac function. Finally, correlations between HP genotypes in different age groups and cardiac manifestations suggest that HP polymorphism could influence the prognosis of this infectious disease. This study shows some of the relevant aspects of the haptoglobin gene polymorphism and its implications in the T. cruzi infection.

  5. Delay discounting and response disinhibition under acute experimental stress in women with borderline personality disorder and adult attention deficit hyperactivity disorder.

    Science.gov (United States)

    Krause-Utz, A; Cackowski, S; Daffner, S; Sobanski, Esther; Plichta, Michael M; Bohus, M; Ende, G; Schmahl, C

    2016-11-01

    Impulsivity is a core feature of borderline personality disorder (BPD) and attention deficit hyperactivity disorder (ADHD). In BPD, impulsive behavior primarily occurs under acute stress; impulse control deficits under non-stress conditions may be partly related to co-morbid ADHD. We aimed to investigate whether acute experimental stress has an impact on self-reported impulsivity, response inhibition (action withholding, action cancelation) and delay discounting in BPD compared to ADHD. Thirty female BPD patients, 28 female ADHD patients (excluding patients with co-morbid BPD and ADHD), and 30 female healthy controls (HC) completed self-reports and behavioral measures of impulsivity (IMT, assessing action withholding; GoStop, measuring action cancelation, Delay Discounting Task) under baseline conditions and after an experimental stress induction (Mannheim Multicomponent Stress Test). Both patient groups reported higher impulsivity than HC, ADHD reported higher trait impulsivity than BPD. On the IMT, ADHD showed significant action-withholding deficits under both conditions, while BPD performed significantly worse than HC under stress. In BPD but not ADHD and HC, action-withholding deficits (IMT) were significantly increased under stress compared to baseline, while no group/stress effects were found for action cancelation (GoStop). Delay discounting was significantly more pronounced in BPD than in HC (no stress effect was found). In BPD, behavioral deficits in action withholding (but not in action cancelation) appear to be influenced by acute experimental stress. Delay discounting seems to be a general feature of BPD, independent of co-morbid ADHD and acute stress, possibly underlying typical expressions of behavioral impulsivity in the disorder.

  6. Delayed administration of allogeneic cardiac stem cell therapy for acute myocardial infarction could ameliorate adverse remodeling: experimental study in swine.

    Science.gov (United States)

    Crisostomo, Veronica; Baez-Diaz, Claudia; Maestre, Juan; Garcia-Lindo, Monica; Sun, Fei; Casado, Javier G; Blazquez, Rebeca; Abad, Jose L; Palacios, Itziar; Rodriguez-Borlado, Luis; Sanchez-Margallo, Francisco M

    2015-05-12

    The optimal timing of cardiac stem cells administration is still unclear. We assessed the safety of same-day and delayed (one week) delivery and the possible influence of the timing on the therapeutic outcomes of allogeneic porcine cardiac stem cells administration after acute myocardial infarction in a closed-chest ischemia-reperfusion model. Female swine surviving 90 min occlusion of the mid left anterior descending coronary artery received an intracoronary injection of 25x10(6) porcine cardiac stem cells either two hours (n = 5, D0) or 7 days (n = 6, D7) after reperfusion. Controls received intracoronary injection of vehicle on day 7 (n = 6, CON). Safety was defined in terms of absence of major cardiac events, changes to the ECG during injection, post-administration coronary flow assessed using the TIMI scale and cardiac troponin I determination after the intervention. Cardiac Magnetic Resonance was performed for morphological and functional assessment prior to infarction, before injection (D7 and CON groups only), at one and 10 weeks. Samples were taken from the infarct and transition areas for pathological examination. No major adverse cardiac events were seen during injection in any group. Animals receiving the therapy on the same day of infarction (D0 group) showed mild transient ST changes during injection (n = 4) and, in one case, slightly compromised coronary flow (TIMI 2). Cardiac function parameters and infarct sizes were not significantly different between groups, with a trend towards higher ejection fraction in the treated groups. Ventricular volumes indexed to body surface area increased over time in control animals, and decreased by the end of the study in animals receiving the therapy, significantly so when comparing End Diastolic Volume between CON and D7 groups (CON: 121.70 ml/m(2) ± 26.09 ml/m(2), D7: 98.71 ml/m(2) ± 8.30 ml/m(2), p = 0.037). The treated groups showed less organization of the collagenous scar, and a significantly (p = 0

  7. Incrimination of Eratyrus cuspidatus (Stal) in the transmission of Chagas' disease by molecular epidemiology analysis of Trypanosoma cruzi isolates from a geographically restricted area in the north of Colombia

    OpenAIRE

    Dib, J.; Barnabé, Christian; Tibayrenc, Michel; Triana, O.

    2009-01-01

    Following the report of two cases of acute Chagas' disease and the appearance of several triatomine species in human dwellings in an area considered non-endemic for domestic transmission of Trypanosoma cruzi; a epidemiological, entomological and T cruzi molecular epidemiology analysis was performed in order to establish the transmission dynamic of the parasite in the studied area. 2 T cruzi isolates from human patients, 5 from Eratyrus cuspidatus, 4 from Rhodnius pallescens, 4 from Panstrongy...

  8. Amebic cysteine proteinase 2 (EhCP2) plays either a minor or no role in tissue damage in acute experimental amebic liver abscess in hamsters.

    Science.gov (United States)

    Olivos-García, Alfonso; González-Canto, Augusto; López-Vancell, Rosario; García de León, Maria del Carmen; Tello, Eusebio; Nequiz-Avendaño, Mario; Montfort, Irmgard; Pérez-Tamayo, Ruy

    2003-06-01

    Amebic cysteine protease 2 (EhCP2) was purified from ethyl ether extracts of axenically grown trophozoites of Entamoeba histolytica strain HM1-IMSS. The purification procedure involved molecular filtration and electroelution. Sequence analysis of the purified product revealed EhCP2 and ubiquitin(s). Electrophoretic migration patterns, isoelectric point determination and Western blot studies failed to reveal other EhCP molecules. Polyclonal antibodies against the purified EhCP2 prepared in rabbits either stabilized or enhanced the enzyme activity in a dose-response manner. Purified EhCP2 was enclosed within inert resin microspheres (22-44 microm in diameter) and injected into the portal vein of normal hamsters. In the liver, the microspheres caused mild acute inflammation and occasional minimal necrosis of short duration. Sections of the liver were immunohistochemically stained with the anti-EhCP2 antibody and the microspheres were positive for only a very short period (1 h) after injection. Sections of experimental acute (1 day, 5 days) amebic liver abscess produced in hamsters were also stained with the anti-EhCP2 antibody; and amebas were intensely positive but no staining was observed at any time in the surrounding necrotic structures. It is suggested that EhCP2 plays either a minor or no role in the causation of tissue damage in experimental acute liver amebiasis.

  9. Health-related quality of life in patients with Chagas disease: a review of the evidence

    Directory of Open Access Journals (Sweden)

    Giovane Rodrigo Sousa

    2015-04-01

    Full Text Available Chagas disease (ChD, a neglected tropical disease caused by infection with the parasite Trypanosoma cruzi (T. cruzi, remains a serious public health issue in Latin America and is an emerging disease in several non-endemic countries, where knowledge of the condition and experience with its clinical management are limited. Regionally, the disease is the major cause of disability secondary to tropical diseases in young adults. Health-related quality of life (HRQoL impairment is common in patients with ChD, especially in those with Chagas dilated cardiomyopathy, the most severe manifestation of the disease, which frequently leads to heart failure. The aim of this review was to conduct a literature search for studies that have evaluated the determining factors of HRQoL in ChD patients. We included cross-sectional, case-control, cohort, and experimental studies, as well as clinical trials that evaluated the HRQoL in ChD patients aged 18 to 60 years and are presenting an explicit description of statistical analysis. Using a combination of keywords based on Descriptors in Health Sciences (DeCS and Medical Subject Headings (MeSH for searches in PubMed and the Scientific Electronic Library Online (SciELO, 148 studies were found. After exclusions, 12 studies were selected for analysis. Three main findings were extracted from these studies: 1 cardiac involvement is associated with a worse HRQoL in ChD patients; 2 HRQoL is associated with the patients' functional capacity; and 3 simple and inexpensive therapeutic measures are effective for improving HRQoL in ChD patients. Hence, ChD patients' functional capacity, the effectiveness of non-surgical conservative treatment, and cardiac involvement are important determining factors for the HRQoL in ChD patients.

  10. [Prevalence of Chagas disease among pregnant women in the southern region of Rio Grande do Sul].

    Science.gov (United States)

    Araújo, Anelise Bergmann; Castagno, Victor Delpizzo; Gallina, Tiago; Berne, Maria Elisabeth Aires

    2009-01-01

    Anti-Trypanosoma cruzi antibodies in the umbilical cord of 351 parturients in the city of Pelotas, Rio Grande do Sul were investigated to determine the prevalence of Chagas disease among pregnant women. One case was identified (0.3%), without detection of congenital transmission. This highlights the importance of investigating Chagas disease among pregnant women living in or originating from endemic areas.

  11. Fungi & Health: can polysaccharides from the fungus inonotus obliquus (CHAGA) inhibit tumor growth?

    DEFF Research Database (Denmark)

    Wold, C. W.; Corthay, A.; Kjeldsen, Christian

    cancer. The last few decades, studies have found Chaga to contain biologically active substances such as polysaccharides, triterpenoids, polyphenols and melanin. In vivo effects such as tumor growth inhibition have been observed in mice receiving various Chaga extracts. The main hypothesis behind...

  12. Chagas disease and systemic autoimmune diseases among Bolivian patients in Switzerland

    Directory of Open Access Journals (Sweden)

    Yves Jackson

    2018-02-01

    Full Text Available BACKGROUND Chronic cardiomyopathy occurs in 20-40% of the patients with Chagas disease. Autoimmune mechanisms may contribute to its pathogenesis. We diagnosed several cases of systemic autoimmune diseases among Bolivian migrants in Geneva with a high prevalence of Chagas disease. OBJECTIVES We tested the hypothesis of a clinical association between systemic autoimmune diseases and Chagas disease, particularly with the development of cardiomyopathy. METHODS We retrospectively searched the medical records of all Bolivian patients visiting Geneva University Hospitals between 2012 and 2015 for diagnosis of Chagas disease or systemic autoimmune diseases. FINDINGS Of the 2,189 eligible patients, 28 [1.3%; 95% confidence interval (CI = 0.9-1.9%] presented with systemic autoimmune disease. The Chagas status was known in 903 (41.3% patient, of whom 244 (27.0%; 95% CI = 24.2-30.0% were positive. Eight (28.6%; 95% CI = 15.3-47.1% of the 28 cases of systemic autoimmune disease had Chagas disease. We found no association between both entities (p = 1.000 or with Chagasic cardiomyopathy (p = 0.729. Moreover, there was no evidence of a temporal relationship between antiparasitic chemotherapy and the development of systemic autoimmune diseases. CONCLUSIONS Our results do not support a clinical association between chronic Chagas disease and systemic autoimmune diseases. However, prospective studies in areas endemic for Chagas disease should better assess the prevalence of systemic autoimmune diseases and thus a possible relationship with this infection.

  13. De ziekte van Chagas in Nederland: een schatting van het aantal patiënten

    NARCIS (Netherlands)

    Bart, Aldert; Hodiamont, Caspar J.; Grobusch, Martin P.; van den Brink, Reneé B. A.; Smout, André J. P. M.; van Gool, Tom

    2011-01-01

    A total of 8-10 million persons are infected worldwide with Trypanosoma cruzi, the causative parasite of Chagas disease, most of whom are inhabitants of Latin America. Due to the increased migration of peoples, Chagas disease has been on the uprise outside Latin America, including in Europe. The

  14. Prevention of congenital Chagas disease by Benznidazole treatment in reproductive-age women. An observational study.

    Science.gov (United States)

    Álvarez, María G; Vigliano, Carlos; Lococo, Bruno; Bertocchi, Graciela; Viotti, Rodolfo

    2017-10-01

    Since the decline in new cases of infection by insect/vector, congenital Chagas disease has become more relevant in the transmission of Chagas disease. Treatment with benznidazole significantly reduces the parasitemia, which constitutes an important factor linked to vertical transmission. The objective of this study was to evaluate whether treatment with benznidazole previously administered to women of childbearing age can prevent or reduce the incidence of new cases of congenital Chagas disease. An historical cohort study that included all women in reproductive age (15-45 years) assisted in our center was designed. We included 67 mothers with chronic Chagas disease; 35 women had not been treated prior to pregnancy, 15 had been treated prior to pregnancy and 17 gave birth prior and after treatment with benznidazole. Eight mothers gave birth to 16 children with congenital Chagas disease (8/67, 12%). The prevalence of congenital Chagas was 16/114 (14%) children born to untreated mothers and 0/42 (0%) children born to benznidazole- treated mothers, p=0.01. No significant differences were observed in clinical, serologic, epidemiological or socioeconomic baseline variables between mothers with and without children born with congenital Chagas. A 32% conversion rate to negative serology was observed in benznidazole-treated women after long-term follow up. Antiparasitic treatment administered to women in reproductive age can prevent the occurrence of congenital Chagas disease. Copyright © 2017 Elsevier B.V. All rights reserved.

  15. Multicenter epidemiological and clinical study on imported Chagas diseases in Alicante, Spain

    NARCIS (Netherlands)

    Ramos, J.M.; Torrus, D.; Amador, C.; Jover, F.; Perez-Chacon, F.; Ponce, Y.; Arjona, F.J.; Caro, E.; Martinez-Peinado, C.; Gallegos, I.; Cuadrado, J.M.; Tello, A.; Gutierrez, F.

    2012-01-01

    Recently, there has been an increase in the number of patients with Chagas disease outside of areas that are generally considered endemic. The aim of this investigation is to describe the clinical profile of a series of patients with Chagas disease in Alicante, Spain, which is a province located on

  16. Chagas disease and systemic autoimmune diseases among Bolivian patients in Switzerland.

    Science.gov (United States)

    Jackson, Yves; Pula, Drenusha Vieira de Mello; Finckh, Axel; Chizzolini, Carlo; Chappuis, François

    2018-02-05

    Chronic cardiomyopathy occurs in 20-40% of the patients with Chagas disease. Autoimmune mechanisms may contribute to its pathogenesis. We diagnosed several cases of systemic autoimmune diseases among Bolivian migrants in Geneva with a high prevalence of Chagas disease. We tested the hypothesis of a clinical association between systemic autoimmune diseases and Chagas disease, particularly with the development of cardiomyopathy. We retrospectively searched the medical records of all Bolivian patients visiting Geneva University Hospitals between 2012 and 2015 for diagnosis of Chagas disease or systemic autoimmune diseases. Of the 2,189 eligible patients, 28 [1.3%; 95% confidence interval (CI) = 0.9-1.9%] presented with systemic autoimmune disease. The Chagas status was known in 903 (41.3%) patient, of whom 244 (27.0%; 95% CI = 24.2-30.0%) were positive. Eight (28.6%; 95% CI = 15.3-47.1%) of the 28 cases of systemic autoimmune disease had Chagas disease. We found no association between both entities (p = 1.000) or with Chagasic cardiomyopathy (p = 0.729). Moreover, there was no evidence of a temporal relationship between antiparasitic chemotherapy and the development of systemic autoimmune diseases. Our results do not support a clinical association between chronic Chagas disease and systemic autoimmune diseases. However, prospective studies in areas endemic for Chagas disease should better assess the prevalence of systemic autoimmune diseases and thus a possible relationship with this infection.

  17. Evaluation of Right Ventricular Systolic Function in Chagas Disease Using Cardiac Magnetic Resonance Imaging.

    Science.gov (United States)

    Moreira, Henrique T; Volpe, Gustavo J; Marin-Neto, José A; Ambale-Venkatesh, Bharath; Nwabuo, Chike C; Trad, Henrique S; Romano, Minna M D; Pazin-Filho, Antonio; Maciel, Benedito C; Lima, João A C; Schmidt, André

    2017-03-01

    Right ventricular (RV) impairment is postulated to be responsible for prominent systemic congestion in Chagas disease. However, occurrence of primary RV dysfunction in Chagas disease remains controversial. We aimed to study RV systolic function in patients with Chagas disease using cardiac magnetic resonance. This cross-sectional study included 158 individuals with chronic Chagas disease who underwent cardiac magnetic resonance. RV systolic dysfunction was defined as reduced RV ejection fraction based on predefined cutoffs accounting for age and sex. Multivariable logistic regression was used to verify the relationship of RV systolic dysfunction with age, sex, functional class, use of medications for heart failure, atrial fibrillation, and left ventricular systolic dysfunction. Mean age was 54±13 years, 51.2% men. RV systolic dysfunction was identified in 58 (37%) individuals. Although usually associated with reduced left ventricular ejection fraction, isolated RV systolic dysfunction was found in 7 (4.4%) patients, 2 of them in early stages of Chagas disease. Presence of RV dysfunction was not significantly different in patients with indeterminate/digestive form of Chagas disease (35.7%) compared with those with Chagas cardiomyopathy (36.8%) ( P =1.000). In chronic Chagas disease, RV systolic dysfunction is more commonly associated with left ventricular systolic dysfunction, although isolated and early RV dysfunction can also be identified. © 2017 American Heart Association, Inc.

  18. Acute effects of intracranial hypertension and ARDS on pulmonary and neuronal damage: a randomized experimental study in pigs.

    Science.gov (United States)

    Heuer, Jan Florian; Pelosi, Paolo; Hermann, Peter; Perske, Christina; Crozier, Thomas A; Brück, Wolfgang; Quintel, Michael

    2011-07-01

    To determine reciprocal and synergistic effects of acute intracranial hypertension and ARDS on neuronal and pulmonary damage and to define possible mechanisms. Twenty-eight mechanically ventilated pigs were randomized to four groups of seven each: control; acute intracranial hypertension (AICH); acute respiratory distress syndrome (ARDS); acute respiratory distress syndrome in combination with acute intracranial hypertension (ARDS + AICH). AICH was induced with an intracranial balloon catheter and the inflation volume was adjusted to keep intracranial pressure (ICP) at 30-40 cmH2O. ARDS was induced by oleic acid infusion. Respiratory function, hemodynamics, extravascular lung water index (ELWI), lung and brain computed tomography (CT) scans, as well as inflammatory mediators, S100B, and neuronal serum enolase (NSE) were measured over a 4-h period. Lung and brain tissue were collected and examined at the end of the experiment. In both healthy and injured lungs, AICH caused increases in NSE and TNF-alpha plasma concentrations, extravascular lung water, and lung density in CT, the extent of poorly aerated (dystelectatic) and atelectatic lung regions, and an increase in the brain tissue water content. ARDS and AICH in combination induced damage in the hippocampus and decreased density in brain CT. AICH induces lung injury and also exacerbates pre-existing damage. Increased extravascular lung water is an early marker. ARDS has a detrimental effect on the brain and acts synergistically with intracranial hypertension to cause histological hippocampal damage.

  19. The Effect of Some 4,2 and 5,2 Bisthiazole Derivatives on Nitro-Oxidative Stress and Phagocytosis in Acute Experimental Inflammation

    Directory of Open Access Journals (Sweden)

    Cătălin Araniciu

    2014-07-01

    Full Text Available Nineteen bisthiazoles were tested in order to assess their anti-inflammatory and antioxidant properties. First, we evaluated the in vitro direct antioxidant capacity of the bisthiazoles using the DPPH radical scavenging method. Then, the anti-inflammatory effect was tested in acute rat experimental inflammation by measuring the acute phase bone marrow response, the phagocytic capacity and the serum nitro-oxidative stress status. Although none of the substances showed significant direct antioxidant potential in the DPPH assay, most of them improved serum oxidative status, when administered to rats with inflammation. Four of the bisthiazoles proved to have good anti-inflammatory properties, similar or superior to that of equal doses meloxicam.

  20. ITIH4 (inter-alpha-trypsin inhibitor heavy chain 4) is a new acute-phase protein isolated from cattle during experimental infection

    DEFF Research Database (Denmark)

    Pineiro, M.; Andres, M.; Iturralde, M.

    2004-01-01

    , and Peptostreptococcus indolicus to induce an acute-phase reaction. All animals developed moderate to severe clinical mastitis and exhibited remarkable increases in ITIH4 concentration in serum (from 3 to 12 times the initial values, peaking at 48 to 72 h after infection) that correlated with the severity of the disease....... Animals with experimental infections with bovine respiratory syncytial virus (BRSV) also showed increases in ITIH4 concentration (from two- to fivefold), which peaked at around 7 to 8 days after inoculation. Generally, no response was seen after a second infection of the same animals with the virus....... Because of the significant induction of the protein in the animals in the mastitis and BRSV infection models, we can conclude that ITIH4 is a new positive acute-phase protein in cattle....

  1. Identifying spatial data availability and spatial data needs for Chagas disease mitigation in South America.

    Science.gov (United States)

    Morris, Emily; Bone, Christopher

    2016-05-01

    The objective of this paper on Chagas disease is to determine the availability and spatial resolution of existing data that can be used to address Chagas disease transmission risk in South America. A literature review was conducted to determine prominent variables that models utilize to assist with efforts to mitigate Chagas disease. Next, a Web search was performed to collect publicly available spatial data pertaining to these variables for the countries in South America. The data were classified based on type and spatial extent, which were then used to create maps of data availability of variables related to Chagas disease transmission. Governments can use this information to better direct their resources to collect data and control the spread of triatomines and Chagas more effectively, and potentially identify more cost-effective strategies for eliminating triatomine vectors. Copyright © 2016 Elsevier Ltd. All rights reserved.

  2. From Lemongrass to Ivermectin: Ethnomedical Management of Chagas Disease in Tropical Bolivia.

    Science.gov (United States)

    Forsyth, Colin

    2017-07-31

    Chagas disease is a neglected tropical disease; the only viable drugs are outdated and produce frequent side effects, and the overwhelming majority of cases are undiagnosed and untreated. Globally, people encounter numerous impediments to accessing biomedical treatment for Chagas disease. However, little is known about how people with Chagas disease manage their health outside the biomedical system. In this article, I discuss knowledge of ethnomedical treatments among marginalized patients in an endemic area of Bolivia. I interviewed 68 patients, 63 (93 percent) of whom had positive diagnoses for Chagas disease. Participants free listed 66 ethnomedical remedies either for Chagas disease (n = 39) or its cardiac symptoms. Participants stressed the accessibility of ethnomedical remedies in contrast to the multiple barriers to accessing biomedical treatment. Far from eroding in the face of globalization and sociopolitical marginalization, ethnomedical knowledge in the study area is dynamic and flexible, communicated through various channels.

  3. Challenges in the management of Chagas disease in Latin-American migrants in Europe.

    Science.gov (United States)

    Monge-Maillo, B; López-Vélez, R

    2017-05-01

    Chagas disease is endemic in Latin America. Due to migration the infection has crossed borders and it is estimated that 68,000-120,000 people with Chagas disease are currently living in Europe and 30% of them may develop visceral involvement. However, up to 90% of Chagas disease cases in Europe remain undiagnosed. The challenges which have to be overcome in Chagas disease in non-endemic countries are focused on related downing barriers to health care access, and related to screening, diagnostic tools and therapeutic management. The aim of this review is to highlight how healthcare management for Latin American migrants with Chagas disease in Europe may be improved. Medical literature was searched using PubMed. No limits were placed with respect to the language or date of publication although most of the articles selected were articles published in the last five years. Chosen search terms were "Chagas disease" AND ("migrants" OR "screening" OR "transmission" OR "treatment"; OR "knowledge" OR "non-endemic countries"); migrants AND ("Public health" OR "Health Service Accessibility" OR "Delivery of Health care"); and "Congenital Chagas disease". Healthcare management of migrant populations with Chagas disease in Europe has to be improved: -Surveillance programmes are needed to measure the burden of the disease; -screening programmes are needed; -administrative and cultural barriers in the access to health care for migrants should be reduced; -education programmes on Chagas disease should be performed -research on new diagnostic tools and therapeutic options are required. This review highlights the needs of profound changes in the health care of Latin American migrants with Chagas disease in Europe. Copyright © 2017 European Society of Clinical Microbiology and Infectious Diseases. Published by Elsevier Ltd. All rights reserved.

  4. Acute phase response elicited by experimental bovine diarrhea virus (BVDV) infection is associated with decreased vitamin D and E status of vitamin-replete preruminant calves.

    Science.gov (United States)

    Nonnecke, B J; McGill, J L; Ridpath, J F; Sacco, R E; Lippolis, J D; Reinhardt, T A

    2014-09-01

    Studies in young animals have shown an association between vitamin deficiencies and increased risk of infectious disease; however, there is a paucity of information regarding the effect of acute infection on the vitamin status of the vitamin-replete neonate. To characterize the effects of acute infection on vitamin D and E status of the neonate, 6 vitamin-replete preruminant Holstein bull calves were experimentally infected with bovine viral diarrhea virus (BVDV; strain BVDV2-1373). Six mock-inoculated calves served as controls. Sustained pyrexia, leukopenia, and asynchronous increases in serum haptoglobin and serum amyloid A characterized the response of calves to infection with BVDV. Infection was also associated with increased serum IFN-γ, IL-2, and IL-6 concentrations. During the last 8 d of the 14-d postinoculation period, serum 25-hydroxyvitamin D and α-tocopherol concentrations in infected calves decreased by 51 and 82%, respectively. The observed inverse association between vitamin D and E status and serum amyloid A in infected calves suggests that the infection-induced acute phase response contributed to the reduced vitamin status of these animals. Additional studies are necessary to determine if the negative effect of infection on status are unique to this specific infection model or is representative of preruminant calf's response to acute infection. Studies are also needed to characterize mechanisms underlying infection-related changes in vitamin D and E status and to determine whether additional vitamin D or E supplementation during an acute infection diminishes disease severity and duration in the young animal. Copyright © 2014 American Dairy Science Association. Published by Elsevier Inc. All rights reserved.

  5. Level of the proteins of the acute phase as criterions of the antibacterial therapy effectiveness in the E.coli associated experimental peritonitis

    Directory of Open Access Journals (Sweden)

    V. V. Minukhin

    2013-08-01

    Full Text Available Introduction. Peritonitis is accompanied by increase of acute-phase proteins levels. C – reactive protein (CRP is acute – phase protein which is produced in human organism in response to tissue injury, infection or inflammation. CRP is produced in small quantities (<1mg/l under normal conditions. Measurement of CRP levels in serum is used for setting of the diagnosis and diseases monitoring as well as efficacy of their treatment. Seromucoid (orosomucoid, alpha-1 acid glucoprotein is one of acute – phase proteins. Levels of serum orosomucoid are elevated since onset of the inflammatory process due to microbial contamination develops in peritonitis. Levels of alpha – 1 acid glucoprotein is elevated during acute phase of inflammation. Alpha – 1 acid glucoprotein is one of main acute – phase proteins. Aim of the study. To determinate levels of seromucoid and CRP in serum of experimental animals and to evaluate the duration of the inflammatory process and the efficacy of antimicrobial therapy in mice with experimentally induced peritonitis. Material and methods of study. Levels of CRP were determined with the use of a half – quantitative immunoturbidimetric method. Levels of seromucoids were determined by means of the immunoturbidimetric method. Levels of CRP and seromucoid were determined in serum obtained from mice in which experimental peritonitis were induced by Escherichia coli. Mice were divided into 6 groups depending on methods of treatment: the 1st group: Amikacin; the 2nd group: gatifloxacin; the 3rd group: Amikacin combined with Gatiflocsacin; the 4th group: Amikacin combined with Bacteriophagum Coli-Proteicum; the 5th group: Gatiflocsacin combined with Bacteriophagum Coli-Proteicum; the 6th group: Amikacin combined with Gatiflocsacin and Bacteriophagum Coli-Proteicum; Studies were conducted on the 3rd and the 5th day after the start of antimicrobial therapy. Results of study. Studies showed that the positive CRP test and the

  6. Evidence for a role of mitogen-activated protein kinases in the treatment of experimental acute pancreatitis.

    Science.gov (United States)

    Irrera, Natasha; Bitto, Alessandra; Interdonato, Monica; Squadrito, Francesco; Altavilla, Domenica

    2014-11-28

    Acute pancreatitis (AP) is an inflammatory disease characterized by acute inflammation and necrosis of the pancreatic parenchyma. AP is often associated with organ failure, sepsis, and high mortality. The pathogenesis of AP is still not well understood. In recent years several papers have highlighted the cellular and molecular events of acute pancreatitis. Pancreatitis is initiated by activation of digestive enzymes within the acinar cells that are involved in autodigestion of the gland, followed by a massive infiltration of neutrophils and macrophages and release of inflammatory mediators, responsible for the local and systemic inflammatory response. The hallmark of AP is parenchymal cell necrosis that represents the cause of the high morbidity and mortality, so that new potential therapeutic approaches are indispensable for the treatment of patients at high risk of complications. However, not all factors that determine the onset and course of the disease have been explained. Aim of this article is to review the role of mitogen-activated protein kinases in pathogenesis of acute pancreatitis.

  7. The liver protective effect of methylprednisolone on a new experimental acute-on-chronic liver failure model in rats.

    Science.gov (United States)

    Hu, Chao; Shen, Shiqiang; Zhang, Aimin; Ren, Bo; Lin, Fusheng

    2014-10-01

    Acute-on-chronic liver failure is a severe, life-threatening entity and the comprehension of this disease is incomplete. Currently, a reasonable surgical model of acute-on-chronic liver failure is still lacking. The aim of this study was to establish a new model of acute-on-chronic liver failure in rats and to investigate the protective effects of methylprednisolone on this model. An obstructive jaundice model in rats was established. Two weeks later, the animals were subjected to a choledochoduodenostomy and a reduced-size hepatic ischaemia/reperfusion injury. Animals were randomly divided into a control group, a methylprednisolone injected via the tail vein group and a methylprednisolone injected via the portal vein group. The survival rates and serum levels of alanine transaminase, aspartate aminotransferase, total bilirubin, tumour necrosis factor alpha, and interferon gamma of the rats were measured and the pathological changes in liver tissues were observed. The survival rate was significantly improved in the methylprednisolone treatment groups. Serum levels of the biochemical indexes were the lowest in the portal vein injection group. Liver tissues under microscopy presented severe pathological injury in the control group. This model could be useful for further research into acute-on-chronic liver failure and methylprednisolone may be a potential therapeutic agent for this disease. Copyright © 2014 Editrice Gastroenterologica Italiana S.r.l. Published by Elsevier Ltd. All rights reserved.

  8. The experimental investigation of fibrinolytic system under the influence of flocalin in conditions of acute hypoxic kidney injury

    Directory of Open Access Journals (Sweden)

    A. I. Gozhenko

    2017-08-01

    Full Text Available In the experiments on rats subjected to acute hypoxic histochemical nephropathy, caused by sodium nitrite and 2,4-dinitrophenol, fibrinolytic activities of blood plasma, urine, renal cortex, medulla, and papilla after treatment with flocalin – the activator of KATP channels, were studied­. It was shown that in the conditions of acute kidney hypoxic injury flocalin administration resulted in the increase and essential restoration of fibrinolysis in blood plasma diminished under hypoxia, which was due to the growth of non-enzymatic fibrinolysis, whereas in urine and renal medulla the appreciable increase of enzymatic fibrinolytic activity took place. Moreover, the treatment of hypoxic nephropathy animals by flocalin resulted in the marked restoration of kidney ion regulatory and protein excretory functions that proves the positive influence of KATP channels activation on the one of the biochemical mechanisms of acute kidney injury as well as the protective effect of flocalin in relation to tubular cells of nephron. The obtained results testify to the beneficial effects of KATP channels activation in the conditions of acute hypoxic kidneys injury.

  9. Diagnostic value of plasma signal peptide-Cub-Egf domain-containing protein-1 (SCUBE-1) in an experimental model of acute ischemic stroke.

    Science.gov (United States)

    Turkmen, Suha; Eryigit, Umut; Karaca, Yunus; Mentese, Ahmet; Sumer, Uzun Aysegul; Yulug, Esin; Aksut, Nurhak; Gazioglu, Sibel; Gunduz, Abdulkadir

    2015-02-01

    This study was intended to examine possible diagnostic value of plasma Signal Peptide-Cub-Egf domain-containing protein-1 (SCUBE1) levels in an experimental model of acute ischemic stroke. Twenty-four female Sprague Dawley rats were divided into four groups. Blood and brain tissue specimens were collected immediately following artery ligation (control; Group 1), 1h after ligation (Group 2), 2 h after ligation (Group 3) and 6h after ligation (Group 4). SCUBE1 levels were investigated in the serum specimens. The brain samples were examined histopathologically. Correlation analysis was performed between the values. Median SCUBE1 values were 1.75 ng/ml in the control group, 3.80 ng/ml, 3.71 ng/ml and 4.19 ng/ml in the groups 2, 3 and 4, respectively (n=6 for each, P=0.004, for each group compared to control values). Histopathological analysis revealed median atrophic neuron percentages of 16% (in group 1), 42%, 55% and 76% in group 2, 3 and 4 respectively (n=6 for each, P=0.004, for each group compared to control group). A higly significant correlation was determined between SCUBE-1 levels and percentage of atrophic neurons (r=0.744 P=0.000). In this experimental model of acute ischemic stroke plasma SCUBE1 levels rose from the 1st hour of induced stroke and remained high up to 6th hour tested. Results of this experimental study has a potential to become the basis for a clinical study to confirm whether SCUBE1 can be used as a biomarker in the early diagnosis of acute ischemic stroke patients. Copyright © 2014 Elsevier Inc. All rights reserved.

  10. [Experimental substantiation of use of sodium hypochlorite and ozone at a formation of intestinal anastomosis in conditions of acute intestinal obstruction and peritonitis].

    Science.gov (United States)

    Lelianov, A D; Ivliev, N V; Bazhenov, S M; Nesterov, A A

    2009-01-01

    Presented are the results of experimental research on 144 animals (the rats Wistar), on whom was carried out resection of a part of large intestine and a intestinal anastamosis was formed in the presents of acute intestinal obstruction and peritonitis. The sanitation of abdominal cavity in the basic group of animals (74) was performed using sodium hypochlorite solution and dissolved ozone. The intestinal lavage was carried out by dissolved ozone with the subsequent introduction of ozonized oil Ozonide in the area of intestinal anastamosis. The combined application of ozone and sodium produces an expressed samative effect which leads to healing of intestinal anastamosis and decreases unstability of intestinal sutures and mortality.

  11. Chagas disease diagnostic applications: present knowledge and future steps

    Science.gov (United States)

    Balouz, Virginia; Agüero, Fernán; Buscaglia, Carlos A.

    2017-01-01

    Chagas disease, caused by the protozoan Trypanosoma cruzi, is a life-long and debilitating illness of major significance throughout Latin America, and an emergent threat to global public health. Being a neglected disease, the vast majority of Chagasic patients have limited access to proper diagnosis and treatment, and there is only a marginal investment into R&D for drug and vaccine development. In this context, identification of novel biomarkers able to transcend the current limits of diagnostic methods surfaces as a main priority in Chagas disease applied research. The expectation is that these novel biomarkers will provide reliable, reproducible and accurate results irrespective of the genetic background, infecting parasite strain, stage of disease, and clinical-associated features of Chagasic populations. In addition, they should be able to address other still unmet diagnostic needs, including early detection of congenital T. cruzi transmission, rapid assessment of treatment efficiency or failure, indication/prediction of disease progression and direct parasite typification in clinical samples. The lack of access of poor and neglected populations to essential diagnostics also stress the necessity of developing new methods operational in Point-of-Care (PoC) settings. In summary, emergent diagnostic tests integrating these novel and tailored tools should provide a significant impact on the effectiveness of current intervention schemes and on the clinical management of Chagasic patients. In this chapter, we discuss the present knowledge and possible future steps in Chagas disease diagnostic applications, as well as the opportunity provided by recent advances in high-throughput methods for biomarker discovery. PMID:28325368

  12. Chagas Disease Diagnostic Applications: Present Knowledge and Future Steps.

    Science.gov (United States)

    Balouz, V; Agüero, F; Buscaglia, C A

    2017-01-01

    Chagas disease, caused by the protozoan Trypanosoma cruzi, is a lifelong and debilitating illness of major significance throughout Latin America and an emergent threat to global public health. Being a neglected disease, the vast majority of Chagasic patients have limited access to proper diagnosis and treatment, and there is only a marginal investment into R&D for drug and vaccine development. In this context, identification of novel biomarkers able to transcend the current limits of diagnostic methods surfaces as a main priority in Chagas disease applied research. The expectation is that these novel biomarkers will provide reliable, reproducible and accurate results irrespective of the genetic background, infecting parasite strain, stage of disease, and clinical-associated features of Chagasic populations. In addition, they should be able to address other still unmet diagnostic needs, including early detection of congenital T. cruzi transmission, rapid assessment of treatment efficiency or failure, indication/prediction of disease progression and direct parasite typification in clinical samples. The lack of access of poor and neglected populations to essential diagnostics also stresses the necessity of developing new methods operational in point-of-care settings. In summary, emergent diagnostic tests integrating these novel and tailored tools should provide a significant impact on the effectiveness of current intervention schemes and on the clinical management of Chagasic patients. In this chapter, we discuss the present knowledge and possible future steps in Chagas disease diagnostic applications, as well as the opportunity provided by recent advances in high-throughput methods for biomarker discovery. Copyright © 2017 Elsevier Ltd. All rights reserved.

  13. Efeitos hemodinâmicos da sobrecarga ventricular direita aguda experimental Efectos hemodinámicos de la sobrecarga ventricular derecha aguda experimental Hemodynamic effects of experimental acute right ventricular overload

    Directory of Open Access Journals (Sweden)

    Flávio Brito Filho

    2011-04-01

    el estudio, siendo divididos en 4 grupos: uno control, no sometido a la oclusión vascular pulmonar, y tres de sobrecarga ventricular derecha sometidos a la oclusión de las siguientes arterias pulmonares: SVD1 (arteria pulmonar izquierda; SVD2 (arteria pulmonar izquierda y del lóbulo inferior derecho y SVD3 (arteria pulmonar izquierda, del lóbulo inferior derecho y del lóbulo mediastinal, obstruyendo la vasculatura pulmonar en 42, 76 y 82,0% respectivamente. Variables de hemodinámica fueron medidas cada 15 minutos durante una hora del estudio. En el análisis estadístico, fueron utilizados ajustes de modelos lineares mixtos con estructura de variancias y covariancias. RESULTADOS:En las comparaciones intergrupales, hubo aumento significativo de la frecuencia cardíaca (p = 0,004, presión arterial pulmonar media (p = 0,001 y presión capilar pulmonar (p BACKGROUND: Acute right ventricular overload is associated with high morbidity and mortality clinical situations such as: extensive lung resection, pulmonary thromboembolism, lung transplantation and high altitude pulmonary edema. Some points of its pathophysiology remain unclear. OBJECTIVE: To assess the hemodynamic effects of experimental acute right ventricular overload in pigs. METHODS: Right ventricular overload was induced through the occlusion of the pulmonary arteries using ligationss. Twenty pigs were used in the study, divided into 04 groups: one control group not subject to pulmonary vascular occlusion, and three right ventricular overload groups subject to occlusion of the following pulmonary arteries: SVD1 (left pulmonary artery; SVD2 (left pulmonary artery and right lower lobe and SVD3 (left pulmonary artery, right lower lobe and mediastinal lobe, obstructing the pulmonary vasculature in 42, 76 and 82.0% respectively. Hemodynamic variables were measured every 15 minutes during one hour of study. The statistical analysis employed mixed linear models with variance and covariance structures. RESULTS

  14. Increased osmotic sensitivity for antidiuretic response in chronic chagas' disease

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    Joel Paulo Russomano Veiga

    1985-06-01

    Full Text Available The osmotic threshold for attaining the antidiuretic response to hypertonic saline infusion and Progressive dehydration was studied in 31 patients with the chronic form of Chagas' disease and 16 control patients. The chagasic patients exhibited enhanced osmoticsensitivity to the antidiuretic response. This was demonstrated by lower values of the increments in plasma osmolarity sufficient to induce a significant fall in water clearance, without alterations in the osmolar clearance or creatinine excretion. The time needed to attain the antidiuretic response was shorterfor chagasics in relation to normal subjects. The results suggest the existence of a disturbance in the fine control of osmoregulation in the chagasic patients. They are interpreted to be a consequence of the denervation in hypothalamic or extrahypothalamic areas that regulate the secretion of vasopressin in chronic Chagas' disease.O limiar de sensibilidade osmótíca para obtenção de resposta antídiurética foi avaliado em 31 pacientes com a forma crônica da moléstia de Chagas, através de infusão de salina hipertônica ou desidratação. Os resultados, quando comparados com os obtidos em 16 pacientes-controle, mostram uma sensibilidade osmótíca aumentada para os chagásicos, dados os menores valores do incremento na osmolaridade plasmática, suficiente para induzir uma queda significativa na depuração de água livre, sem alterações na depuração osmolar ou na excreção de creatínina. Também, o tempo necessário para atingir a antídiurese foi mais curto para os chagásicos do que para os controles. Os resultados sugerem a existência de um distúrbio na osmorregulação, nos pacientes chagásicos, caracterizado por uma sensibilidade osmótíca aumentada dos osmorreceptores para liberação da vasopressina. Estes dados interpretam-se como conseqüente à desnervação em áreas hipotalâmicas ou extra-hipotalâmicas, relacionadas com a secreção do horm

  15. Chagas' achalasia treated by a jejunal interposed segment.

    Science.gov (United States)

    Dantas, A N; Carvalho, J L; Coelho, F K; Teixeira, A M; Lyra, L G; Rebouças, G; Didier, F V

    1975-01-01

    Resection of the achalasic area and replacement by a segment of jejunal loop, associated with vagotomy and pyloroplasty, has been performed in 21 patients. The majority of these patients had Chagas' disease, with a dilated esophagus wider than 7 cm. This surgical procedure offered symptomatic relief in 20 of our 21 cases. One patient died, but the death was not necessarily related to the operation. Although disphagia and regurgitation did not disappear entirely in all cases the decrease in severity of these symptoms was such to allow the few symptomatic patients to lead an entirely normal life after the operation.

  16. [The morphometric characteristics of the main structural components of renal nephrons in the white rats with experimentally induced acute and chronic alcohol intoxication].

    Science.gov (United States)

    Shcherbakova, V M

    2016-01-01

    The objective of the present work was to study the morphometric characteristics of the main structural components of renal nephrons in the white rats with the experimentally induced acute and chronic alcohol intoxication. We undertook the morphometric examination of the structural elements of rat kidneys with the subsequent statistical analysis of the data obtained. The results of the study give evidence of the toxic action of ethanol on all structural components of the nephron in the case of both acute and chronic alcohol intoxication. The study revealed some specific features of the development of pathological process in the renal tissue structures at different stages of alcohol intoxication. The most pronounced morphological changes were observed in the renal proximal tubules and the least pronounced ones in the structure of the renal glomeruli. The earliest morphological changes become apparent in distal convoluted tubules of the nephron; in the case of persistent alcoholemia, they first develop in the renal corpuscles and thereafter in the distal proximal tubules. The maximum changes occur in the case of acute alcohol intoxication and between 2 weeks and 2 months of chronic intoxication; they become less conspicuous during a later period.

  17. Modulatory effects of cod liver oil on the antioxidant status and oxidative stress induced by acute exposure to carbon tetrachloride (CCL4) in experimental animal models.

    Science.gov (United States)

    Omugba, Abam Esther; Ajiboye, Adebayo J; Oyagbemi, Ademola A; Agofure, Eze

    2015-05-01

    This work was designed to investigate the modulatory effects of cod liver oil on the acute exposure to carbon tetrachloride (CCL4) in experimental animal models. Markers of oxidative stress, enzymic and non-enzymic antioxidants were assessed in the liver and kidney. The results showed significant (poil compared to the control and CCL4-treated groups. Acute exposure to CCL4 also significantly (preactive substances in the liver of rats treated with cod liver oil compared to the CCL4-treated rats. The reduced glutathione (GSH) content in the liver of the rats administered with CCL4 decreased significantly compared to that in all other treatment groups, whereas rats pretreated and co-administered with cod liver oil and CCl4 showed significant (poil compared to the CCl4 only-treated group. The percentage inhibition of superoxide dismutase (SOD) increased (poil compared to the CCL4-treated rats and the control. Taken together, cod liver oil attenuates CCL4-induced toxicity and oxidative stress in the liver but not in the kidney of rats acutely exposed to CCL4.

  18. Voltammetric behavior of nitrofurazone and its hydroxymethyl prodrug with potential anti-Chagas activity

    Energy Technology Data Exchange (ETDEWEB)

    La-Scalea, Mauro Aquiles [Sao Paulo Univ., SP (Brazil). Faculdade de Ciencias Farmaceuticas; Sao Paulo Univ., SP (Brazil). Inst. de Quimica]. E-mail: scalea@usp.br; Menezes, Carla Maria de Souza; Ferreira, Elizabeth Igne [Sao Paulo Univ., SP (Brazil). Faculdade de Ciencias Farmaceuticas; Juliao, Murilo Sergio da Silva [Sao Paulo Univ., SP (Brazil). Inst. de Quimica; Universidade Estadual Vale do Acaraju, Fortaleza, CE (Brazil). Centro de Ciencias Exatas e Tecnologicas; Man Chin Chung [UNESP, Araraquara, SP (Brazil). Faculdade de Ciencias Farmaceuticas; Serrano, Silvia Helena Pires [Sao Paulo Univ., SP (Brazil). Inst. de Quimica

    2005-07-15

    Chagas' disease is a serious health problem for Latin America. The situation is worsened by the lack of efficient chemotherapy. The two available commercial drugs, benznidazole and nifurtimox, are more effective in the acute phase of the disease. Nitrofurazone is active against Trypanosoma cruzi, however its high toxicity precludes its current use in parasitosis. Hydroxymethyl nitrofurazone is a prodrug of nitrofurazone. It is more active against Trypanosoma cruzi than nitrofurazone, besides being less toxic. This work shows the voltammetric behavior of nitrofurazone and a comparison with those of metronidazole and chloramphenicol using cyclic, linear sweep and differential pulse voltammetries. For these drugs also the prediction of the diffusion coefficients using Wilke-Chang equation was performed. The reduction of nitrofurazone is pH-dependent and in acidic medium the hydroxylamine derivative, involving four electrons, is the principal product formed. In aqueous-alkaline medium and with a glassy carbon electrode pre-treatment the reduction of nitrofurazone occurs in two steps, the first involving one electron to form the nitro-radical anion and the second corresponding to the hydroxylamine derivative formation. Hydroxymethyl nitrofurazone presented the same voltammetric behavior and electroactivity, indicating that the molecular modification performed in nitrofurazone did not change its capacity to be reduced. A brief discussion regarding the differences in biological activity between the two compounds is also presented. (author)

  19. Expression of Bax Protein and Morphological Changes in the Myocardium in Experimental Acute Pressure Overload of the Left Ventricle.

    Science.gov (United States)

    Blagonravov, M L; Korshunova, A Yu; Azova, M M; Bryk, A A; Frolov, V A

    2016-06-01

    The expression of Bax protein, marker of intracellular pathway of apoptosis initiation, in viable left ventricular cardiomyocytes and morphological changes in the myocardium in acute pressure overload of the left ventricle were studied in experiment on male rabbits. The content of Bax protein in the cardiomyocyte cytoplasm decreased, this indicating that the mitochondrial pathway was not involved in the realization of the apoptotic program. This decrease was associated with manifest destructive changes in the left ventricular myocardium.

  20. Influence of matrix nature on the functional efficacy of biomedical cell product for the regeneration of damaged liver (experimental model of acute liver failure

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    S. V. Gautier

    2017-01-01

    Full Text Available Aim. A comparative analysis of the functional efficacy of biomedical cell products (BMCP for the regeneration of damaged liver based on biopolymer scaffolded porous and hydrogel matrices was performed on the experimental model of acute liver failure. Materials and methods. Matrices allowed for clinical use were employed for BMCP in the form of a sponge made from biopolymer nanostructured composite material (BNCM based on a highly purified bacterial copolymers of poly (β-hydroxybutyrate-co-β-oxyvalerate and polyethylene glycol and a hydrogel matrix from biopolymer microheterogeneous collagen-containing hydrogel (BMCH. Cellular component of BMCP was represented by liver cells and multipotent mesenchymal bone marrow stem cells. The functional efficacy of BMCP for the regeneration of damaged liver was evaluated on the experimental model of acute liver failure in Wistar rats (n = 40 via biochemical, morphological, and immunohistochemical methods. Results. When BMCP was implanted to regenerate the damaged liver on the basis of the scaffolded BNCM or hydrogel BMCH matrices, the lethality in rats with acute liver failure was absent; while in control it was 66.6%. Restoration of the activity of cytolytic enzyme levels and protein-synthetic liver function began on day 9 after modeling acute liver failure, in contrast to the control group, where recovery occurred only by days 18–21. Both matrices maintained the viability and functional activity of liver cells up to 90 days with the formation of blood vessels in BMCP. The obtained data confirm that scaffolded BNCM matrix and hydrogel BMCH matrix retain for a long time (up to 90 days the vital activity of the adherent cells in the BMCP composition, which allows using them to correct acute liver failure. At the same time, hydrogel matrix due to the presence of bioactive components contributes to the creation of the best conditions for adhesion and cell activity which accelerate the regeneration processes

  1. A comparison of the clinical and experimental characteristics of four acute surgical pain models: dental extraction, bunionectomy, joint replacement, and soft tissue surgery.

    Science.gov (United States)

    Singla, Neil K; Desjardins, Paul J; Chang, Phoebe D

    2014-03-01

    When a clinical trial of an analgesic produces a negative finding, it is important to consider the influence (if any) of experimental error on the validity of that result. Although efforts to identify and minimize experimental error in chronic pain investigations have begun in earnest, less work has been performed on the optimization of acute pain methodology. Of the acute surgical pain methodology articles that have been published over the last decade, almost all focus on either the dental or bunion model. Analgesics are typically evaluated in a variety of surgical models that eventually include hospital-based models (eg, joint replacement and soft tissue surgery). Every surgical procedure has unique clinical characteristics that must be considered to optimize study design and conduct. Much of the methodological knowledge garnered from bunion and dental studies is applicable to other surgical models, but some extrapolations are hazardous. The purposes of this review were (1) to qualitatively describe the clinical and experimental characteristics of the 4 classic surgical models: dental extraction, bunionectomy, joint replacement, and soft tissue surgery; and (2) to quantitatively compare the models by analyzing 3 factors: effect size, enrollment rate, and demographics. We found that the dental extraction and bunionectomy models had higher assay sensitivity than the joint replacement and soft tissue surgery models. It is probable that this finding is secondary to the superior experimental conditions under which the dental and bunion models are executed (utilization of few centers that have the ability to reduce surgical, anesthetic, and postoperative confounders). Copyright © 2013 International Association for the Study of Pain. Published by Elsevier B.V. All rights reserved.

  2. Chagas disease awareness among Latin American immigrants living in Los Angeles, California.

    Science.gov (United States)

    Sanchez, Daniel R; Traina, Mahmoud I; Hernandez, Salvador; Smer, Aiman M; Khamag, Haneen; Meymandi, Sheba K

    2014-11-01

    Approximately 300,000 persons have Chagas disease in the United States, although almost all persons acquired the disease in Latin America. We examined awareness of Chagas disease among Latin American immigrants living in Los Angeles, California. We surveyed 2,677 persons (age range = 18-60 years) in Los Angeles who resided in Latin America for at least six months. A total of 62% of the participants recalled seeing triatomines in Latin America, and 27% of the participants reported triatomine bites at least once per year while living abroad. A total of 86% of the participants had never heard of Chagas disease. Of persons who had heard of Chagas disease, 81% believed that it was not serious. More than 95% of those who had heard of Chagas disease would want to be tested and treated. Most Latin American immigrants living in Los Angeles recalled exposure to vectors of Chagas disease. However, they have little knowledge of this disease. Increasing awareness of Chagas disease is needed in this high-risk population. © The American Society of Tropical Medicine and Hygiene.

  3. Chagas Disease Awareness among Latin American Immigrants Living in Los Angeles, California

    Science.gov (United States)

    Sanchez, Daniel R.; Traina, Mahmoud I.; Hernandez, Salvador; Smer, Aiman M.; Khamag, Haneen; Meymandi, Sheba K.

    2014-01-01

    Approximately 300,000 persons have Chagas disease in the United States, although almost all persons acquired the disease in Latin America. We examined awareness of Chagas disease among Latin American immigrants living in Los Angeles, California. We surveyed 2,677 persons (age range = 18–60 years) in Los Angeles who resided in Latin America for at least six months. A total of 62% of the participants recalled seeing triatomines in Latin America, and 27% of the participants reported triatomine bites at least once per year while living abroad. A total of 86% of the participants had never heard of Chagas disease. Of persons who had heard of Chagas disease, 81% believed that it was not serious. More than 95% of those who had heard of Chagas disease would want to be tested and treated. Most Latin American immigrants living in Los Angeles recalled exposure to vectors of Chagas disease. However, they have little knowledge of this disease. Increasing awareness of Chagas disease is needed in this high-risk population. PMID:25200261

  4. Effects on Pulmonary Vascular Mechanics of Two Different Lung-Protective Ventilation Strategies in an Experimental Model of Acute Respiratory Distress Syndrome.

    Science.gov (United States)

    Santos, Arnoldo; Gomez-Peñalver, Eva; Monge-Garcia, M Ignacio; Retamal, Jaime; Borges, João Batista; Tusman, Gerardo; Hedenstierna, Goran; Larsson, Anders; Suarez-Sipmann, Fernando

    2017-11-01

    To compare the effects of two lung-protective ventilation strategies on pulmonary vascular mechanics in early acute respiratory distress syndrome. Experimental study. University animal research laboratory. Twelve pigs (30.8 ± 2.5 kg). Acute respiratory distress syndrome was induced by repeated lung lavages and injurious mechanical ventilation. Thereafter, animals were randomized to 4 hours ventilation according to the Acute Respiratory Distress Syndrome Network protocol or to an open lung approach strategy. Pressure and flow sensors placed at the pulmonary artery trunk allowed continuous assessment of pulmonary artery resistance, effective elastance, compliance, and reflected pressure waves. Respiratory mechanics and gas exchange data were collected. Acute respiratory distress syndrome led to pulmonary vascular mechanics deterioration. Four hours after randomization, pulmonary vascular mechanics was similar in Acute Respiratory Distress Syndrome Network and open lung approach: resistance (578 ± 252 vs 626 ± 153 dyn.s/cm; p = 0.714), effective elastance, (0.63 ± 0.22 vs 0.58 ± 0.17 mm Hg/mL; p = 0.710), compliance (1.19 ± 0.8 vs 1.50 ± 0.27 mL/mm Hg; p = 0.437), and reflection index (0.36 ± 0.04 vs 0.34 ± 0.09; p = 0.680). Open lung approach as compared to Acute Respiratory Distress Syndrome Network was associated with improved dynamic respiratory compliance (17.3 ± 2.6 vs 10.5 ± 1.3 mL/cm H2O; p mechanics similarly. The use of higher positive end-expiratory pressures in the open lung approach strategy did not worsen pulmonary vascular mechanics, improved lung mechanics, and gas exchange but at the expense of a lower cardiac index.

  5. A Multi-species Bait for Chagas Disease Vectors

    Science.gov (United States)

    Mota, Theo; Vitta, Ana C. R.; Lorenzo-Figueiras, Alicia N.; Barezani, Carla P.; Zani, Carlos L.; Lazzari, Claudio R.; Diotaiuti, Liléia; Jeffares, Lynne; Bohman, Björn; Lorenzo, Marcelo G.

    2014-01-01

    Background Triatomine bugs are the insect vectors of Trypanosoma cruzi, the etiological agent of Chagas disease. These insects are known to aggregate inside shelters during daylight hours and it has been demonstrated that within shelters, the aggregation is induced by volatiles emitted from bug feces. These signals promote inter-species aggregation among most species studied, but the chemical composition is unknown. Methodology/Principal Findings In the present work, feces from larvae of the three species were obtained and volatile compounds were identified by solid phase microextraction-gas chromatography-mass spectrometry (SPME-GC-MS). We identified five compounds, all present in feces of all of the three species: Triatoma infestans, Panstrongylus megistus and Triatoma brasiliensis. These substances were tested for attractivity and ability to recruit insects into shelters. Behaviorally active doses of the five substances were obtained for all three triatomine species. The bugs were significantly attracted to shelters baited with blends of 160 ng or 1.6 µg of each substance. Conclusions/Significance Common compounds were found in the feces of vectors of Chagas disease that actively recruited insects into shelters, which suggests that this blend of compounds could be used for the development of baits for early detection of reinfestation with triatomine bugs. PMID:24587457

  6. Chagas disease in dogs from endemic areas of Costa Rica.

    Science.gov (United States)

    Montenegro, Victor M; Jimenez, Maurico; Dias, J C Pinto; Zeledon, Rodrigo

    2002-06-01

    Dogs with the presumptive diagnosis of Chagas disease are commonly sent to our School of Veterinary Medicine by independent veterinarians. This prompted us to evaluate the prevalence of canine trypanosomiasis in some villages of the Central Valley of Costa Rica. A total of 54 dogs (21 males and 33 females) from five rural villages, with ages between 3 months and 10 years old, were bled and submitted to three serological tests: indirect immunofluorescence, indirect hemagglutination and ELISA. Among all animals, 15 (27.7%) revealed antibodies (6 pure bred and 9 mongrels) and in 3 of them the parasite was also demonstrated by xenodiagnosis. All positive animals except 1, and 9 negative animals (control group) were examined by X-rays and electrocardiography, revealing different degrees of cardiomegaly and ECG alteration, consistent with Chagas disease pathology in one dog (SA-11) of the infected ones. Examination of 50 inhabitants living in the houses where dogs and Triatoma dimidiata were found, yielded negative serological reactions. This was assumed to support the hypothesis that dogs are commonly infected by the oral route, a more effective means of infection compared with the vector transmission mechanism that occurs in humans.

  7. Chagas Disease in Dogs from Endemic Areas of Costa Rica

    Directory of Open Access Journals (Sweden)

    Montenegro Victor M

    2002-01-01

    Full Text Available Dogs with the presumptive diagnosis of Chagas disease are commonly sent to our School of Veterinary Medicine by independent veterinarians. This prompted us to evaluate the prevalence of canine trypanosomiasis in some villages of the Central Valley of Costa Rica. A total of 54 dogs (21 males and 33 females from five rural villages, with ages between 3 months and 10 years old, were bled and submitted to three serological tests: indirect immunofluorescence, indirect hemagglutination and ELISA. Among all animals, 15 (27.7% revealed antibodies (6 pure bred and 9 mongrels and in 3 of them the parasite was also demonstrated by xenodiagnosis. All positive animals except 1, and 9 negative animals (control group were examined by X-rays and electrocardiography, revealing different degrees of cardiomegaly and ECG alteration, consistent with Chagas disease pathology in one dog (SA-11 of the infected ones. Examination of 50 inhabitants living in the houses where dogs and Triatoma dimidiata were found, yielded negative serological reactions. This was assumed to support the hypothesis that dogs are commonly infected by the oral route, a more effective means of infection compared with the vector transmission mechanism that occurs in humans.

  8. Squalene synthase as a target for Chagas disease therapeutics.

    Directory of Open Access Journals (Sweden)

    Na Shang

    2014-05-01

    Full Text Available Trypanosomatid parasites are the causative agents of many neglected tropical diseases and there is currently considerable interest in targeting endogenous sterol biosynthesis in these organisms as a route to the development of novel anti-infective drugs. Here, we report the first x-ray crystallographic structures of the enzyme squalene synthase (SQS from a trypanosomatid parasite, Trypanosoma cruzi, the causative agent of Chagas disease. We obtained five structures of T. cruzi SQS and eight structures of human SQS with four classes of inhibitors: the substrate-analog S-thiolo-farnesyl diphosphate, the quinuclidines E5700 and ER119884, several lipophilic bisphosphonates, and the thiocyanate WC-9, with the structures of the two very potent quinuclidines suggesting strategies for selective inhibitor development. We also show that the lipophilic bisphosphonates have low nM activity against T. cruzi and inhibit endogenous sterol biosynthesis and that E5700 acts synergistically with the azole drug, posaconazole. The determination of the structures of trypanosomatid and human SQS enzymes with a diverse set of inhibitors active in cells provides insights into SQS inhibition, of interest in the context of the development of drugs against Chagas disease.

  9. Urban transmission of Chagas disease in Cochabamba, Bolivia

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    N Medrano-Mercado

    2008-08-01

    Full Text Available Chagas disease is a major public health problem in Bolivia. In the city of Cochabamba, 58% of the population lives in peripheral urban districts ("popular zones" where the infection prevalence is extremely high. From 1995 to 1999, we studied the demographics of Chagas infections in children from five to 13 years old (n = 2218 from the South zone (SZ and North zone (NZ districts, which differ in social, environmental, and agricultural conditions. Information gathered from these districts demonstrates qualitative and quantitative evidence for the active transmission of Trypanosoma cruzi in urban Cochabamba. Seropositivity was high in both zones (25% in SZ and 19% in NZ. We observed a high risk of infection in children from five to nine years old in SZ, but in NZ, a higher risk occurred in children aged 10-13, with odds ratio for infection three times higher in NZ than in SZ. This difference was not due to triatomine density, since more than 1,000 Triatoma infestans were captured in both zones, but was possibly secondary to the vector infection rate (79% in SZ and 37% in NZ. Electrocardiogram abnormalities were found to be prevalent in children and pre-adolescents (SZ = 40%, NZ = 17%, indicating that under continuous exposure to infection and re-infection, a severe form of the disease may develop early in life. This work demonstrates that T. cruzi infection should also be considered an urban health problem and is not restricted to the rural areas and small villages of Bolivia.

  10. Clinical and nutritional profile of individuals with chagas disease

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    Juliana Geraix

    Full Text Available Chagas disease (CD, caused by the protozoan Trypanossoma cruzi, affects approximately 18 million individuals in the Americas, 5 million of which live in Brazil. Most chronic sufferers have either the indeterminate form of the disease, without organic compromise, or the cardiac or digestive forms. Despite the importance of this disease, there is no information on the effect of nutrition on CD evolution. We evaluated the clinical-nutritional profile of individuals with CD treated at the Tropical Diseases Nutrition Out-Patient Clinic of the Botucatu School of Medicine, UNESP. A retrospective cohort study was performed between 2002 and 2006, on 66 patients with serum and parasitological diagnosis of CD. Epidemiological, clinical, nutritional, and biochemical data were collected, including gender, age, skin color, smoking, alcoholism, physical activity, weight, stature, body mass index, abdominal circumference, glycemia, and lipid profile. Fifty-three percent were male and 47% female; 96% were white skinned. Mean age was 49.6±6.36 years. The predominant form was indeterminate in 71%; smoking and drinking were recorded in 23% and 17%, respectively. Sedentariness predominated in 83%, and 55% presented increased abdominal circumference. Most, 94%, were overweight or obese. The biochemical exams revealed hyperglycemia in 12% and dyslipidemia in 74%. These findings suggest that the Chagas population presents co-morbidities and risk factors for developing chronic non-transmissible diseases, including cardiovascular diseases, making CD evolution even worse.

  11. Clinical and nutritional profile of individuals with Chagas disease.

    Science.gov (United States)

    Geraix, Juliana; Ardisson, Lidiane Paula; Marcondes-Machado, Jussara; Pereira, Paulo Câmara Marques

    2007-08-01

    Chagas disease (CD), caused by the protozoan Trypanossoma cruzi, affects approximately 18 million individuals in the Americas, 5 million of which live in Brazil. Most chronic sufferers have either the indeterminate form of the disease, without organic compromise, or the cardiac or digestive forms. Despite the importance of this disease, there is no information on the effect of nutrition on CD evolution. We evaluated the clinical-nutritional profile of individuals with CD treated at the Tropical Diseases Nutrition Out-Patient Clinic of the Botucatu School of Medicine, UNESP. A retrospective cohort study was performed between 2002 and 2006, on 66 patients with serum and parasitological diagnosis of CD. Epidemiological, clinical, nutritional, and biochemical data were collected, including gender, age, skin color, smoking, alcoholism, physical activity, weight, stature, body mass index, abdominal circumference, glycemia, and lipid profile. Fifty-three percent were male and 47% female; 96% were white skinned. Mean age was 49.6 +/- 6.36 years. The predominant form was indeterminate in 71%; smoking and drinking were recorded in 23% and 17%, respectively. Sedentariness predominated in 83%, and 55% presented increased abdominal circumference. Most, 94%, were overweight or obese. The biochemical exams revealed hyperglycemia in 12% and dyslipidemia in 74%. These findings suggest that the Chagas population presents co-morbidities and risk factors for developing chronic non-transmissible diseases, including cardiovascular diseases, making CD evolution even worse.

  12. Chagas y SIDA, la importancia del diagnóstico precoz

    OpenAIRE

    Sergio R. Auger; Rubén Storino; Miguel De Rosa; Oscar Caravello; González, María I; Edgardo Botaro; Liliana Bonelli; Oscar Rossini

    2005-01-01

    Objetivos: Evaluar las vías de contagio, la reactivación y la evolución de la enfermedad de Chagas en pacientes con HIV. Material y métodos Se incorporaron pacientes internados con SIDA y Chagas reactivo. Se evaluaron la epidemiología, la adicción a drogas, la reactivación de la enfermedad de Chagas y el órgano blanco más afectado, la demora del inicio de tratamiento antiparasitario y la evolución posterior. Se realizaron serologías, estudios parasitológicos en sangre y líquido cefalorraq...

  13. Acute, sub-chronic oral toxicity studies and evaluation of antiulcer activity of Sooktyn in experimental animals

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    Phool Chandra

    2012-01-01

    Full Text Available Sooktyn (SKN, mineralo-herbal drug which is being used largely by the patients for its extremely good therapeutic value to treat the gastric ulcers. The present study was undertaken to evaluate the toxicity studies and antiulcer activity of SKN. Acute and sub-chronic toxicities were studied in male and female Wistar rats. A single acute SKN of 2 000 mg/kg was administered by oral gavage for acute toxicity. Sub-chronic doses were 400 and 800 mg/kg/day. The major toxicological end points examined included animal body weight and food intake, selected tissue weights, and detailed gross necropsy. In addition, we examined blood elements: hematocrit, hemoglobin concentration, erythrocyte count, total leukocyte count and MCH, MCHC and platelets as well as biochemical parameters: urea, sugar, alanine transaminase, aspartate transaminase, alkaline phosphatase, total proteins, and creatinine. Also, anti-ulcer activity was carried out by employing indomethacin, ethanol, pylorus ligation, and hypothermic-stress-induced ulcer models. LD 50 may be greater than 2 000 mg/kg (orally for SKN and there were no signs of toxicity on 28 days sub-chronic oral administration of 400 and 800 mg/kg of SKN in rats on the basis of blood elements and biochemical parameters. The ulcer indices decrease in all ulcer models with 66.62%, 61.24%, 80.18%, and 74.76% in indomethacin, ethanol, pylorus ligation, and hypothermic-stress-induced ulcer models, respectively. The results suggest that SKN has no signs of toxicity at 2 000 mg/kg body weight of rats orally; sub-chronically. The drug is safe and has antiulcer activity.

  14. Acute, sub-chronic oral toxicity studies and evaluation of antiulcer activity of Sooktyn in experimental animals.

    Science.gov (United States)

    Chandra, Phool; Sachan, Neetu; Kishore, Kamal; Ghosh, Ashoke Kumar

    2012-04-01

    Sooktyn (SKN), mineralo-herbal drug which is being used largely by the patients for its extremely good therapeutic value to treat the gastric ulcers. The present study was undertaken to evaluate the toxicity studies and antiulcer activity of SKN. Acute and sub-chronic toxicities were studied in male and female Wistar rats. A single acute SKN of 2 000 mg/kg was administered by oral gavage for acute toxicity. Sub-chronic doses were 400 and 800 mg/kg/day. The major toxicological end points examined included animal body weight and food intake, selected tissue weights, and detailed gross necropsy. In addition, we examined blood elements: hematocrit, hemoglobin concentration, erythrocyte count, total leukocyte count and MCH, MCHC and platelets as well as biochemical parameters: urea, sugar, alanine transaminase, aspartate transaminase, alkaline phosphatase, total proteins, and creatinine. Also, anti-ulcer activity was carried out by employing indomethacin, ethanol, pylorus ligation, and hypothermic-stress-induced ulcer models. LD(50) may be greater than 2 000 mg/kg (orally) for SKN and there were no signs of toxicity on 28 days sub-chronic oral administration of 400 and 800 mg/kg of SKN in rats on the basis of blood elements and biochemical parameters. The ulcer indices decrease in all ulcer models with 66.62%, 61.24%, 80.18%, and 74.76% in indomethacin, ethanol, pylorus ligation, and hypothermic-stress-induced ulcer models, respectively. The results suggest that SKN has no signs of toxicity at 2 000 mg/kg body weight of rats orally; sub-chronically. The drug is safe and has antiulcer activity.

  15. Unraveling Chagas disease transmission through the oral route: Gateways to Trypanosoma cruzi infection and target tissues.

    Directory of Open Access Journals (Sweden)

    Danielle Silva-Dos-Santos

    2017-04-01

    Full Text Available Oral transmission of Trypanosoma cruzi, the causative agent of Chagas disease, is the most important route of infection in Brazilian Amazon and Venezuela. Other South American countries have also reported outbreaks associated with food consumption. A recent study showed the importance of parasite contact with oral cavity to induce a highly severe acute disease in mice. However, it remains uncertain the primary site of parasite entry and multiplication due to an oral infection. Here, we evaluated the presence of T. cruzi Dm28c luciferase (Dm28c-luc parasites in orally infected mice, by bioluminescence and quantitative real-time PCR. In vivo bioluminescent images indicated the nasomaxillary region as the site of parasite invasion in the host, becoming consistently infected throughout the acute phase. At later moments, 7 and 21 days post-infection (dpi, luminescent signal is denser in the thorax, abdomen and genital region, because of parasite dissemination in different tissues. Ex vivo analysis demonstrated that the nasomaxillary region, heart, mandibular lymph nodes, liver, spleen, brain, epididymal fat associated to male sex organs, salivary glands, cheek muscle, mesenteric fat and lymph nodes, stomach, esophagus, small and large intestine are target tissues at latter moments of infection. In the same line, amastigote nests of Dm28c GFP T. cruzi were detected in the nasal cavity of 6 dpi mice. Parasite quantification by real-time qPCR at 7 and 21 dpi showed predominant T. cruzi detection and expansion in mouse nasal cavity. Moreover, T. cruzi DNA was also observed in the mandibular lymph nodes, pituitary gland, heart, liver, small intestine and spleen at 7 dpi, and further, disseminated to other tissues, such as the brain, stomach, esophagus and large intestine at 21 dpi. Our results clearly demonstrated that oral cavity and adjacent compartments is the main target region in oral T. cruzi infection leading to parasite multiplication at the nasal