scholarly journals Exploring the potential activity spectrum of two 5-nitroindazolinone prototypes on different Trypanosoma cruzi strains

2015 ◽  
Vol 1 ◽  
Author(s):  
CRISTINA FONSECA-BERZAL ◽  
PATRICIA BERNARDINO DA SILVA ◽  
CRISTIANE FRANÇA DA SILVA ◽  
MARIANE VASCONCELOS ◽  
MARCOS MEUSER BATISTA ◽  
...  
Keyword(s):  
Trypanosoma Cruzi ◽  
Chagas Disease ◽  
Primary Cultures ◽  
Human Infection ◽  
Sequential Screening ◽  
Similar Range ◽  
Activity Spectrum ◽  
Potential Activity ◽  
Moderately Resistant

SUMMARYIn the present study, the potential activity of two 5-nitroindazole derivatives previously proposed as suitable antichagasic prototypes was further evaluated on diverseTrypanosoma cruzistrains belonging to two discrete typing units (DTUs) frequently associated with human infection (i.e. DTUs TcII and TcVI). The trypanocidal profile that both 2-benzyl-1-propyl (22) and 2-benzyl-1-butyl (24) derivatives achieved on Tulahuen amastigotes (IC50 = 3·56 ± 0·99 and 6·31 ± 1·04 µm, respectively) correlates with that of formerly obtained on CL Brener, corroborating an outstanding activity on DTU TcVI parasites. Moreover, a sequential screening on extracellular and intracellular stages ofT. cruziY (DTU TcII) demonstrated also the effectiveness of 22 and 24 over this strain on a similar range of activity (IC50epimastigotes = 3·55 ± 0·47 and 7·92 ± 1·63 µm, IC50amastigotes = 2·80 ± 0·46 and 9·02 ± 5·26 µm, respectively). These results, supported by a lack of toxicity registered over either L929 fibroblasts or primary cultures of cardiomyocytes, confirm that 5-nitroindazolinones 22 and 24 display great selectivity on both drug-sensitive (CL and Tulahuen) and drug-moderately resistant (Y)T. cruzistrains, and therefore, represent an important outcome in the research of Chagas disease chemotherapy.

Characterization of human infection by Leishmania spp. in the Northwest of Argentina: immune response, double infection with Trypanosoma cruzi and species of Leishmania involved

Parasitology ◽  
2003 ◽  
Vol 126 (1) ◽  
pp. 31-39 ◽  
Author(s):  
F. M. FRANK ◽  
M. M. FERNÁNDEZ ◽  
N. J. TARANTO ◽  
S. P. CAJAL ◽  
R. A. MARGNI ◽  
...  
Keyword(s):  
Immune Response ◽  
Trypanosoma Cruzi ◽  
Chagas Disease ◽  
Human Infection ◽  
Double Infection ◽  
Strong Immune Response ◽  
American Tegumentary Leishmaniasis ◽  
Leishmania Spp ◽  
Very High

The aims of this study were to characterize human American tegumentary leishmaniasis, which includes cutaneous, mucocutaneous and mucosal leishmaniasis, in Northwest Argentina, to determine the prevalence of double infection with Trypanosoma cruzi and to identify the species of Leishmania in this area. Most of the 330 leishmaniasis patients presented cutaneous ulcers (96·1%), 2·4% mucocutaneous and 1·5% the mucosal form (‘espundia’). The aetiological agents, determined by isoenzyme electrophoresis, were identified as Leishmania (Viannia) braziliensis in 16 out of 20 isolates and in the remaining 4 as Leishmania (Leishmania) amazonensis, the first ever-documented in Argentina. Sera analysed by ELISA and IFA using complex antigen from both T. cruzi and L. braziliensis showed a very high percentage of positives (66·3–78·2%). When antigens for specific diagnosis of Chagas' disease were used, 40·9% of the leishmaniasis patients were also found to be infected by T. cruzi. These results indicate that the strong immune response against T. cruzi gave no protection to Leishmania, in spite of the serological cross-reaction between these parasites. In addition, we showed that more than 40% of the patients would be misdiagnosed as chagasic if complex antigens, as epimastigotes or soluble fraction from epimastigotes, were used in IFA or ELISA. This is of paramount importance not only because patients' treatment would be associated to misdiagnosis but the fact that in many countries in Central and South America, a positive test for Chagas' disease means a rejection for those seeking employment.

scholarly journals A Fluorinated Phenylbenzothiazole Arrests the Trypanosoma cruzi Cell Cycle and Diminishes the Infection of Mammalian Host Cells

2019 ◽  
Vol 64 (2) ◽  
Author(s):  
Roberto I. Cuevas-Hernández ◽  
Richard M. B. M. Girard ◽  
Sarai Martínez-Cerón ◽  
Marcelo Santos da Silva ◽  
Maria Carolina Elias ◽  
...  
Keyword(s):  
Trypanosoma Cruzi ◽  
Chagas Disease ◽  
Structural Characteristics ◽  
Chronic Phase ◽  
Human Infection ◽  
Host Cells ◽  
Mammalian Host ◽  
Content Type ◽  
Trypanocidal Drugs

ABSTRACT Chagas disease (CD) is a human infection caused by Trypanosoma cruzi. CD was traditionally endemic to the Americas; however, due to migration it has spread to countries where it is not endemic. The current chemotherapy to treat CD induces several side effects, and its effectiveness in the chronic phase of the disease is controversial. In this contribution, substituted phenylbenzothiazole derivatives were synthesized and biologically evaluated as trypanocidal agents against Trypanosoma cruzi. The trypanocidal activities of the most promising compounds were determined through systematic in vitro screening, and their modes of action were determined as well. The physicochemical-structural characteristics responsible for the trypanocidal effects were identified, and their possible therapeutic application in Chagas disease is discussed. Our results show that the fluorinated compound 2-methoxy-4-[5-(trifluoromethyl)-1,3-benzothiazol-2-yl] phenol (BT10) has the ability to inhibit the proliferation of epimastigotes [IC50(Epi) = 23.1 ± 1.75 μM] and intracellular forms of trypomastigotes [IC50(Tryp) = 8.5 ± 2.9 μM] and diminishes the infection index by more than 80%. In addition, BT10 has the ability to selectively fragment 68% of the kinetoplastid DNA compared with 5% of nucleus DNA. The mode of action for BT10 on T. cruzi suggests that the development of fluorinated phenylbenzothiazole with electron-withdrawing substituent is a promising strategy for the design of trypanocidal drugs.

Clinical Trypanosoma rangeli infection as a complication of Chagas‘ disease

Parasitology ◽  
1987 ◽  
Vol 94 (3) ◽  
pp. 475-484 ◽  
Author(s):  
F. Guhl ◽  
L. Hudson ◽  
C. J. Marinkelle ◽  
C. A. Jaramillo ◽  
D. Bridge
Keyword(s):  
Trypanosoma Cruzi ◽  
Chagas Disease ◽  
Western Blotting ◽  
Mixed Infections ◽  
Laboratory Studies ◽  
Trypanosoma Rangeli ◽  
Active Infection ◽  
Binding Reaction ◽  
Rio Negro ◽  
Similar Range

Laboratory studies on a group of 20 patients from the Rio Negro Valley, Colombia selected for detailed study showed that 14 gave antibody reactions on immunoassay consistent with Trypanosoma cruzi or T. rangeli infections. Four were diagnosed as having T. rangeli infection, 4 had mixed infections and 6 were infected with T. cruzi alone. Immunoprecipitation analysis showed that sera from T. crwzi-infected patients recognized a similar range of trypomastigote-derived polypeptides as sera from patients in Brazil, and all of the Colombian sera reacted with the 160 kiloDalton (kDa) polypeptide associated with active infection. Although sera from patients with T. rangeli infection alone gave a positive immunofluorescence or ELISA reaction with T. rangeli, they failed to bind to parasite polypeptides by either immunoprecipitation or Western blotting. Intriguingly, sera from patients with mixed infections consistently gave a stronger, but qualitatively similar, binding reaction in immunoprecipitation and Western blotting compared to sera from patients infected with T. cruzi alone.

scholarly journals Reconhecimento de Padrões em Imagens de Triatomíneos Usando Redes Neurais Artificiais com Algoritmo Backpropagation

2020 ◽  
Author(s):  
Joao Marcelino Pacheco Neto ◽  
Otavio Noura Teixeira
Keyword(s):  
Neural Networks ◽  
Image Processing ◽  
Artificial Neural Networks ◽  
Trypanosoma Cruzi ◽  
Chagas Disease ◽  
Digital Image Processing ◽  
Digital Image ◽  
Human Infection ◽  
Classification Of Images

Chagas disease, also known as American trypanosomiasis isone of the consequences of the human infection caused by theflagellate protozoan called Trypanosoma cruzi transmittedby the barbeiro of the subfamily Triatominae known as triatomines.In the Lower Tocantins region of the state of Para,three genera of barbers transmitting the disease are found.Searching for a way to automate the manual recognition process,this work aimed to implement a Model of Recognitionand Classification of Images of barbers found in the LowerTocantins region in order to recognize the genus of the insectthrough the use of Artificial Neural Networks PerceptronMulti-layered and performing training with Backpropagationalgorithm, helping to identify the transmitters. In themiddle of this recognition, the Digital Image Processing isperformed to extract important characteristics relevant to theclassification. This entire process is performed in MATLABsoftware through scripts and the creation of the ArtificialNeural Network in the toolbox called Pattern RecognitionApp.

Dynamics of T Cells Repertoire During Trypanosoma cruzi Infection and its Post-Treatment Modulation

2019 ◽  
Vol 26 (36) ◽  
pp. 6519-6543 ◽  
Author(s):  
Adriana Egui ◽  
Paola Lasso ◽  
Elena Pérez-Antón ◽  
M. Carmen Thomas ◽  
Manuel Carlos López
Keyword(s):  
Immune Response ◽  
Trypanosoma Cruzi ◽  
Chagas Disease ◽  
Cardiac Tissue ◽  
Acute Infection ◽  
Clinical Status ◽  
Chronic Phase ◽  
Parasite Load ◽  
Chronic Patients ◽  
Cruzi Infection

Chagas disease courses with different clinical phases and has a variable clinical presentation and progression. The acute infection phase mostly exhibits a non-specific symptomatology. In the absence of treatment, the acute phase is followed by a chronic phase, which is initially asymptomatic. This chronic asymptomatic phase of the disease is characterized by a fragile balance between the host’s immune response and the parasite replication. The loss of this balance is crucial for the progression of the sickness. The virulence and tropism of the T. cruzi infecting strain together to the inflammation processes in the cardiac tissue are the main factors for the establishment and severity of the cardiomyopathy. The efficacy of treatment in chronic Chagas disease patients is controversial. However, several studies carried out in chronic patients demonstrated that antiparasitic treatment reduces parasite load in the bloodstream and leads to an improvement in the immune response against the Trypanosoma cruzi parasite. The present review is mainly focused on the cellular patterns associated to the clinical status and the evolution of the disease in chronic patients, as well as the effectiveness of the treatment related to T. cruzi infection control. Therefore, an emphasis is placed on the dynamics of specific-antigens T cell subpopulations, their memory and activation phenotypes, their functionality and their contribution to pathogenesis or disease control, as well as their association with risk of congenital transmission of the parasite.

The Prevalence of Trypanosoma cruzi, the Causal Agent of Chagas Disease, in Texas Rodent Populations

EcoHealth ◽  
2017 ◽  
Vol 14 (1) ◽  
pp. 130-143 ◽  
Author(s):  
Adriana Aleman ◽  
Trina Guerra ◽  
Troy J. Maikis ◽  
Matthew T. Milholland ◽  
Ivan Castro-Arellano ◽  
...  
Keyword(s):  
Trypanosoma Cruzi ◽  
Chagas Disease ◽  
Causal Agent ◽  
Rodent Populations

scholarly journals Absence of Bim sensitizes mice to experimental Trypanosoma cruzi infection

2021 ◽  
Vol 12 (7) ◽  
Author(s):  
Marcela Hernández-Torres ◽  
Rogério Silva do Nascimento ◽  
Monica Cardozo Rebouças ◽  
Alexandra Cassado ◽  
Kely Catarine Matteucci ◽  
...  
Keyword(s):  
T Cells ◽  
Trypanosoma Cruzi ◽  
Chagas Disease ◽  
Parasite Load ◽  
Peritoneal Macrophages ◽  
T Cell Response ◽  
No Production ◽  
Similar Reduction ◽  
Ifn Γ

AbstractChagas disease is a life-threatening disorder caused by the protozoan parasite Trypanosoma cruzi. Parasite-specific antibodies, CD8+ T cells, as well as IFN-γ and nitric oxide (NO) are key elements of the adaptive and innate immunity against the extracellular and intracellular forms of the parasite. Bim is a potent pro-apoptotic member of the Bcl-2 family implicated in different aspects of the immune regulation, such as negative selection of self-reactive thymocytes and elimination of antigen-specific T cells at the end of an immune response. Interestingly, the role of Bim during infections remains largely unidentified. To explore the role of Bim in Chagas disease, we infected WT, Bim+/−, Bim−/− mice with trypomastigotes forms of the Y strain of T. cruzi. Strikingly, our data revealed that Bim−/− mice exhibit a delay in the development of parasitemia followed by a deficiency in the control of parasite load in the bloodstream and a decreased survival compared to WT and Bim+/− mice. At the peak of parasitemia, peritoneal macrophages of Bim−/− mice exhibit decreased NO production, which correlated with a decrease in the pro-inflammatory Small Peritoneal Macrophage (SPM) subset. A similar reduction in NO secretion, as well as in the pro-inflammatory cytokines IFN-γ and IL-6, was also observed in Bim−/− splenocytes. Moreover, an impaired anti-T. cruzi CD8+ T-cell response was found in Bim−/− mice at this time point. Taken together, our results suggest that these alterations may contribute to the establishment of a delayed yet enlarged parasitic load observed at day 9 after infection of Bim−/− mice and place Bim as an important protein in the control of T. cruzi infections.

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