Indeterminate Chagas’ disease: Trypanosoma cruzi strain and re-infection are factors involved in the progression of cardiopathy

2003 ◽  
Vol 104 (4) ◽  
pp. 415-420 ◽  
Author(s):  
Juan M. BUSTAMANTE ◽  
Héctor W. RIVAROLA ◽  
Alicia R. FERNÁNDEZ ◽  
Julio E. ENDERS ◽  
Ricardo FRETES ◽  
...  
Keyword(s):  
Survival Rate ◽  
Trypanosoma Cruzi ◽  
Chagas Disease ◽  
Infected Group ◽  
World Health ◽  
Cardiac Lesions ◽  
Health Organization ◽  
Host Parasite ◽  
Β Adrenergic Receptors ◽  
First Time

Chagas' disease is caused by Trypanosoma cruzi, which is transmitted by reduviid bugs. The World Health Organization has estimated that about 16–18 million people in the Americas are infected, and that more than 100 million are at risk. In the present study we have used a murine model to analyse if particular T. cruzi strains (Tulahuen strain and SGO-Z12 isolate from a chronic patient) and/or re-infection may determine, during the indeterminate phase of experimental Chagas' disease, changes that could explain the different evolution of cardiac lesions. Re-infected mice reached higher parasitaemias than those infected for the first time. The survival in the indeterminate phase of mice infected with Tulahuen strain was 50.0%, while the SGO-Z12-infected group presented a significantly higher survival rate (77.1%; P<0.01). The SGO-Z12-re-infected group showed a survival rate (70.9%) significantly higher than that of the Tulahuen-re-infected group (37.0%; P<0.01). Electrocardiographic abnormalities were found in 66% of Tulahuen-infected mice, while in SGO-Z12-infected group such abnormalities were found in only 36% of animals (P<0.01). The two groups exhibited similar percentages of electrocardiographic dysfunction on re-infection, although intraventricular blocks were more frequent in Tulahuen-re-infected mice (P<0.01). Hearts from infected or re-infected mice with either parasite showed mononuclear infiltrates. The SGO-Z12-re-infected and Tulahuen-re-infected groups exhibited a significantly diminished affinity (P<0.05) and a significantly increased density (P<0.05) of cardiac β-adrenergic receptors compared with the infected and non-infected groups. The indeterminate phase of Chagas' disease is defined as a prolonged period that is clinically silent, but the present findings show that different T. cruzi strains and re-infection are able to alter the host–parasite equilibrium, and these factors may be responsible for inducing progressive cardiopathy.

scholarly journals Capsaicin inhibits arginine kinase and exerts anti-Trypanosoma cruzi activity

2020 ◽  
Author(s):  
Edward A. Valera-Vera ◽  
Chantal Reigada ◽  
Melisa Sayé ◽  
Fabio A. Digirolamo ◽  
Mariana R. Miranda ◽  
...  
Keyword(s):  
Trypanosoma Cruzi ◽  
Chagas Disease ◽  
Stress Responses ◽  
Mammalian Cells ◽  
Arginine Kinase ◽  
Chronic Phase ◽  
New Drugs ◽  
World Health ◽  
Neglected Diseases ◽  
Health Organization

ABSTRACTTrypanosoma cruzi is the causative agent of Chagas disease, considered within the list of twenty neglected diseases according to the World Health Organization. There are only two therapeutic drugs for Chagas disease, both of them unsuitable for the chronic phase, therefore the development of new drugs is a priority.T. cruzi arginine kinase (TcAK) is a promising drug target since it is absent in humans and it is involved in cellular stress responses. In a previous study from our laboratory, possible TcAK inhibitors were identified through computer simulations, resulting in the best-scoring compounds cyanidin derivatives and capsaicin. Considering these results, in this work we evaluate the effect of capsaicin on TcAK activity and its trypanocidal effect. Although capsaicin produced a weak inhibition on the recombinant TcAK activity (IC50 ≈ 800 µM), it had a strong trypanocidal effect on epimastigotes and trypomastigotes (IC50 = 6.26 µM and 0.26 µM, respectively) being 20-fold more active on trypomastigotes than mammalian cells. Epimastigotes that overexpress TcAK were 37% more resistant to capsaicin than wild type parasites, suggesting that trypanocidal activity could be due, in part, to the enzyme inhibition. However, the difference between the concentrations at which the enzyme is inhibited and the parasite death is caused implies the presence of other targets. In this sense, the prohibitin-2 and calmodulin were identified as other possible capsaicin targets. Capsaicin is a strong and selective trypanocidal agent active in nanomolar concentrations, with an IC50 57-fold lower than benznidazole, the drug currently used for treating Chagas disease.

Synthesis of New Thiosemicarbazones and Semicarbazones Containing the 1,2,3-1H-triazole-isatin Scaffold: Trypanocidal, Cytotoxicity, Electrochemical Assays, and Molecular Docking

2019 ◽  
Vol 15 (3) ◽  
pp. 240-256 ◽  
Author(s):  
Bianca N.M. Silva ◽  
Policarpo A. Sales Junior ◽  
Alvaro J. Romanha ◽  
Silvane M.F. Murta ◽  
Camilo H.S. Lima ◽  
...  
Keyword(s):  
Molecular Docking ◽  
Trypanosoma Cruzi ◽  
Chagas Disease ◽  
Docking Studies ◽  
World Health ◽  
Neglected Diseases ◽  
Alkyl Aryl ◽  
Development Of Resistance ◽  
Health Organization

Background: Chagas disease, also known as American trypanosomiasis, is classified as one of the 17 most important neglected diseases by the World Health Organization. The only drugs with proven efficacy against Chagas disease are benznidazole and nifurtimox, however both show adverse effects, poor clinical efficacy, and development of resistance. For these reasons, the search for new effective chemical entities is a challenge to research groups and the pharmaceutical industry. Objective: Synthesis and evaluation of antitrypanosomal activities of a series of thiosemicarbazones and semicarbazones containing 1,2,3-1H triazole isatin scaffold. Method: 5&'-(4-alkyl/aryl)-1H-1,2,3-triazole-isatins were prepared by Huisgen 1,3-dipolar cycloaddition and the thiosemicarbazones and semicarbazones were obtained by the 1:1 reactions of the carbonylated derivatives with thiosemicarbazide and semicarbazide hydrochloride, respectively, in methanol, using conventional reflux or microwave heating. The compounds were assayed for in vitro trypanocidal activity against Trypanosoma cruzi, the aetiological agent of Chagas disease. Beyond the thio/semicarbazone derivatives, isatin and triazole synthetic intermediates were also evaluated for comparison. Results: A series of compounds were prepared in good yields. Among the 37 compounds evaluated, 18 were found to be active, in particular thiosemicarbazones containing a non-polar saturated alkyl chain (IC50 = 24.1, 38.6, and 83.2 &µM; SI = 11.6, 11.8, and 14.0, respectively). To further elucidate the mechanism of action of these new compounds, the redox behaviour of some active and inactive derivatives was studied by cyclic voltammetry. Molecular docking studies were also performed in two validated protein targets of Trypanosoma cruzi, i.e., cruzipain (CRZ) and phosphodiesterase C (TcrPDEC). Conclusion: A class of thio/semicarbazones structurally simple and easily accessible was synthesized. Compounds containing thiosemicarbazone moieties showed the best results in the series, being more active than the corresponding semicarbazones. Our results indicated that the activity of these compounds does not originate from an oxidation-reduction pathway but probably from the interactions with trypanosomal enzymes.

Diluted benznidazole decreases side effects in animals infected by Trypanosoma cruzi and treated with benznidazole in ponderal dose

2021 ◽  
Vol 11 (40) ◽  
pp. 170-171
Author(s):  
Denise Lessa Aleixo ◽  
Fabiana Nabarro Ferraz ◽  
Miguel Spack ◽  
Gislaine Janaina S F Temporini ◽  
Camila Fernanda Brustolin ◽  
...  
Keyword(s):  
Side Effects ◽  
Trypanosoma Cruzi ◽  
Chagas Disease ◽  
World Health ◽  
Adherence To Treatment ◽  
Treatment Control ◽  
Treatment Regimens ◽  
Health Organization ◽  
Important Progress ◽  
Better Than

Background: The infection caused by the protozoan Trypanosoma cruzi affects millions of people around the world and the benznidazole is the only drug available for the etiological treatment, despite the fact that its adverse effect makes the adherence to treatment more difficult. Taking advantage of the antiparasitic effect of benznidazole and minimizing its side effects, without causing discomfort symptoms to the patient, would be an important progress in the health care of individuals infected with T. cruzi. Aim: The aim of this study was to evaluate the effect of different treatment regimens using diluted and ponderal benznidazole, associated or not, in murine infection with T. cruzi. Methodology: A hundred male Swiss mice 28 – year – old infected with 1400 blood trypomastigotes of the Y strain of T. cruzi, were used in the experiment, divided into groups according to the treatment: Control (CI) - infected animals treated orally with 7% hydroalcoholic solution (vehicle of product preparation highly diluted) (N = 20); BZp - infected animals treated with BZ in ponderal dose (100 mg/kg/20days) from the detection of the infection (N = 20); BZh - infected animals treated with BZ highly diluted (30x) from the detection of the infection (N = 20), BZp+h - infected animals treated with a combination of BZ highly diluted (30x) + BZ in ponderal dose (100 mg / kg), from the detection of the infection (n= 20); BZp+hT4A - infected animals treated with the association of BZ in ponderal dose (100 mg / kg ) from the detection of the infection and BZ highly diluted (30x) four days after starting the treatment with BZp (N = 20). Clinical (body weight, water and food intake, amount of feces, temperature, aspect of the fur, mortality and survival time) and parasitological (total parasitemia and area under the parasitemia curve) parameters were evaluated. Results: It was observed a reduction of side effects associated with clinical improvement of the animals treated with the combination of BZ in ponderal dose and highly diluted given 4 days after (BZp+hT4A) or concurrently (BZp+h) with the beginning of the treatment with benznidazole in ponderal dose, with results statistically better than those observed in groups BZp, BZh e CI (p0.05). In the group treated only with the BZ ultradiluted (BZh) the parasitemia remained high, resulting in the death of all animals within a period of 20 days as observed in the CI. Conclusions: The reduction of side effects, the improvement of the clinical evolution and non-compromising the parasiticide effect, show that the association of the benznidazole medication in ponderal dose and highly diluted should be further explored. Keywords: Homeopathy, Trypanosoma cruzi, Side effects, Benznidazole References MINISTÉRIO DA SAÁDE. Secretaria de Vigilância em Saúde. Brazilian Consensus on Chagas Disease. Rev. Soc. Bras. Med. Trop. 2005; 38:7-29. WHO. World Health Organization. Sixty-third World Healthy. Assembly. Chagas disease: control and elimination. 2010.

Zinc 1,2,4-triazolo[1,5-a]pyrimidine complexes: synthesis, structural characterization and their effect against Chagas disease

2021 ◽  
Vol 17 ◽  
Author(s):  
José M. Méndez-Arriaga ◽  
Erika Rubio-Mirallas ◽  
Miguel Quirós ◽  
Manuel Sánchez-Moreno
Keyword(s):  
Trypanosoma Cruzi ◽  
Chagas Disease ◽  
New Drugs ◽  
World Health ◽  
Neglected Diseases ◽  
X Ray Diffraction ◽  
X Ray ◽  
Health Organization ◽  
The Third World

Background: The World Health Organization catalogues illnesses such as Chagas disease as neglected diseases, due the low investment in new drugs to fight them. The search for novel and non-side effects anti-parasitic compounds is one of the urgent needs of the Third World. The use of triazolopyrimidines and their metal complexes have demonstrated hopeful results in this field. Objective: This work studies the antiparasitic efficacy against Trypanosoma cruzi strains of a series of zinc triazolopyrimidine complexes. Method: A series of Zn complexes has been synthesized by the reaction between the triazolopyrimidine derivatives 7-amino-1,2,4-triazolo[1,5-a]pyrimidine (7atp) and 5,7-dimethyl-1,2,4-triazolo[1,5-a]pyrimidine (dmtp) with Zn(SO4) • 7H2O, ZnCl2, and Zn(NO3)2 • 6H2O salts. The complexes have been analyzed by spectroscopic and thermal assays and X-ray diffraction methods have been used to dilucidate the crystalline structure of one of them. The antiparasitic efficacy was tested in vitro against Trypanosoma cruzi to compare the trypanocidal effect of different ligands and counteranions to fight Chagas disease. Results: The efficacy of these compounds against Trypanosoma cruzi has also been tested to compare the influence of different ligands and counteranions on the trypanocidal effect against Chagas disease. Conclusion: Antiproliferative tests corroborate the synergistic trypanocidal effect of the triazolopyrimidine coordination complexes.

scholarly journals Panstrongylus diasi Pinto & Lent, 1946 (Hemiptera, Reduviidae, Triatominae): first record in Mato Grosso, Brazil

Check List ◽  
2018 ◽  
Vol 15 (2) ◽  
pp. 259-264
Author(s):  
Mirian Francisca Martins ◽  
Sinara Cristina de Moraes ◽  
Marcos Takashi Obara ◽  
Cleber Galvão
Keyword(s):  
Trypanosoma Cruzi ◽  
Urban Area ◽  
Chagas Disease ◽  
New Record ◽  
First Record ◽  
Mato Grosso ◽  
Host Parasite Interactions ◽  
Host Parasite ◽  
First Time

Panstrongylus diasi Pinto & Lent, 1946, previously known from throught the Brazilian center-west, is reported for the first time in Mato Grosso state, Brazil. We found 3 specimens, 1 of them from an urban area of Barra do Garças. The new record of P. diasi is important for the understanding of the epidemiology of Chagas disease, mainly because this species is found naturally infected with Trypanosoma cruzi (Chagas, 1909). Studies on the ecology, biogeography, and vector–host/parasite interactions of P. diasi are essential.

scholarly journals Programme for Harmonization to the International Scale in Latin America for BCR-ABL1 quantification in CML patients: findings and recommendations

2020 ◽  
Vol 58 (12) ◽  
pp. 2025-2035
Author(s):  
María Sol Ruiz ◽  
María Belén Sánchez ◽  
Yuly Masiel Vera Contreras ◽  
Evangelina Agrielo ◽  
Marta Alonso ◽  
...  
Keyword(s):  
Latin America ◽  
Myeloid Leukemia ◽  
World Health ◽  
Molecular Response ◽  
Limit Of Quantification ◽  
International Scale ◽  
Deep Molecular Response ◽  
Health Organization ◽  
First Time

AbstractObjectivesThe quantitation of BCR-ABL1 mRNA is mandatory for chronic myeloid leukemia (CML) patients, and RT-qPCR is the most extensively used method in testing laboratories worldwide. Nevertheless, substantial variation in RT-qPCR results makes inter-laboratory comparability hard. To facilitate inter-laboratory comparative assessment, an international scale (IS) for BCR-ABL1 was proposed.MethodsThe laboratory-specific conversion factor (CF) to the IS can be derived from the World Health Organization (WHO) genetic reference panel; however, this material is limited to the manufacturers to produce and calibrate secondary reference reagents. Therefore, we developed secondary reference calibrators, as lyophilized cellular material, aligned to the IS. Our purpose was both to re-evaluate the CF in 18 previously harmonized laboratories and to propagate the IS to new laboratories.ResultsOur field trial including 30 laboratories across Latin America showed that, after correction of raw BCR-ABL1/ABL1 ratios using CF, the relative mean bias was significantly reduced. We also performed a follow-up of participating laboratories by annually revalidating the process; our results support the need for continuous revalidation of CFs. All participating laboratories also received a calibrator to determine the limit of quantification (LOQ); 90% of them could reproducibly detect BCR-ABL1, indicating that these laboratories can report a consistent deep molecular response. In addition, aiming to investigate the variability of BCR-ABL1 measurements across different RNA inputs, we calculated PCR efficiency for each individual assay by using different amounts of RNA.ConclusionsIn conclusion, for the first time in Latin America, we have successfully organized a harmonization platform for BCR-ABL1 measurement that could be of immediate clinical benefit for monitoring the molecular response of patients in low-resource regions.

scholarly journals Radon Gas in the City of Alicante. High Risk of Low Indoor Air Quality in Poorly Ventilated Buildings

2020 ◽  
Vol 17 (23) ◽  
pp. 8762
Author(s):  
Carlos Rizo-Maestre ◽  
Víctor Echarri-Iribarren
Keyword(s):  
World Health ◽  
Santa Barbara ◽  
Buried Structures ◽  
Gaseous State ◽  
Major Health ◽  
Radon Gas ◽  
Health Organization ◽  
Measurement Location ◽  
First Time ◽  
The City

In December 2019, Spain considered for the first time the presence of radon to the Technical Building Code (Basic Document HS 6: Radon Exposure Protection), although it only mentions minimum presences and the need for ventilation. This research shows that in buried structures or in places with little ventilation, even in soils with a low probability of granite, a high content of radon gas can be found. The city of Alicante has been used as a measurement location for different architectural sites; here, the level of 100 Bq/m3 is the first threshold where the gas must be monitored, and the level of 300 Bq/m3 is the maximum threshold above which corrective ventilation measures must be taken. The research conducted during the years 2015 and 2016 shows that it is necessary to account for also the areas considered to be “low presence of radon gas” to achieve healthy constructions. The renewal of air in the different places will be tested for the presence of radon, i.e., the greater the accumulation is, the less ventilation and the greater the risk of accumulation of radon gas. This study is located in the city of Alicante, where the seven civil constructions are located: two Civil War shelters, the Santa Barbara Castle, the Ereta Powder Keg, the Luceros-Marq and Serra Grossa railway tunnels and the Británica underground deposits. Radon gas is currently a concern for major health and medical agencies because it is considered to be a chemical element that is very harmful to people. The World Health Organization is one of the organisations that has the objective of studying and researching this element, to develop solutions. Radon gas is normally found in a gaseous state and is highly radioactive. It is present in many terrains and it is mostly found in those with granite; although the presence of this element is very low, there is always a minimum presence. In the past, in nongranite soils, the dose of radon was considered to be so low that it was insignificant. Therefore, in this research, the aim is to consider the high presence of radon gas in nongranite soils as long as the conditions for its accumulation are present.

scholarly journals Structural and functional evidence for membrane docking and disruption sites on phospholipase A2-like proteins revealed by complexation with the inhibitor suramin

2015 ◽  
Vol 71 (10) ◽  
pp. 2066-2078 ◽  
Author(s):  
Guilherme H. M. Salvador ◽  
Thiago R. Dreyer ◽  
Walter L. G. Cavalcante ◽  
Fábio F. Matioli ◽  
Juliana I. dos Santos ◽  
...  
Keyword(s):  
Tertiary Structure ◽  
Biological Effects ◽  
World Health ◽  
Ligand Interaction ◽  
Fatty Acid Binding ◽  
Interaction Sites ◽  
High Resolution Structure ◽  
Health Organization ◽  
First Time

Local myonecrosis resulting from snakebite envenomation is not efficiently neutralized by regular antivenom administration. This limitation is considered to be a significant health problem by the World Health Organization. Phospholipase A2-like (PLA2-like) proteins are among the most important proteins related to the muscle damage resulting from several snake venoms. However, despite their conserved tertiary structure compared with PLA2s, their biological mechanism remains incompletely understood. Different oligomeric conformations and binding sites have been identified or proposed, leading to contradictory data in the literature. In the last few years, a comprehensive hypothesis has been proposed based on fatty-acid binding, allosteric changes and the presence of two different interaction sites. In the present study, a combination of techniques were used to fully understand the structural–functional characteristics of the interaction between suramin and MjTX-II (a PLA2-like toxin).In vitroneuromuscular studies were performed to characterize the biological effects of the protein–ligand interaction and demonstrated that suramin neutralizes the myotoxic activity of MjTX-II. The high-resolution structure of the complex identified the toxin–ligand interaction sites. Calorimetric assays showed two different binding events between the protein and the inhibitor. It is demonstrated for the first time that the inhibitor binds to the surface of the toxin, obstructing the sites involved in membrane docking and disruption according to the proposed myotoxic mechanism. Furthermore, higher-order oligomeric formation by interaction with interfacial suramins was observed, which may also aid the inhibitory process. These results further substantiate the current myotoxic mechanism and shed light on the search for efficient inhibitors of the local myonecrosis phenomenon.

scholarly journals Community Based Chagas Control Program

2018 ◽  
Vol 2 (2) ◽  
Keyword(s):  
Chagas Disease ◽  
Neglected Tropical Diseases ◽  
Control Program ◽  
Poor Quality ◽  
World Health ◽  
Tropical Diseases ◽  
Social Instability ◽  
Main Determinants ◽  
Health Organization ◽  
Effective Transmission

In 2012, World Health Organization published the first ever Neglected Tropical Diseases (NTD) Roadmap, entitled “Accelerating Work to Overcome the Global Impact of Neglected Tropical Diseases: A Roadmap for Implementation.” This report brought international attention to Chagas and other NTDs and provided a framework to guide implementation of policies and strategies set out in the Global Plan to Combat Neglected Tropical Diseases 2008-2015. Chagas disease, endemic to Bolivia, is considered the third most common parasitic disease globally, after malaria and schistosomiasis. It is estimated that six to seven million persons are infected worldwide. [1] Bolivia has the highest rate of endemic Chagas disease in the Americas. Chagas disease is both a disease of poverty and, like other neglected tropical diseases, poverty promoting. [2] Chagas disease is associated with multiple social and environmental determinants in communities marked by poverty. Salient among the main determinants are poor-quality dwellings, social instability, the combined presence of certain environmental factors, such as the Chagas vectors, mammals that serve as reservoirs of the disease and human exposure, creating the conditions for perpetuating the effective transmission of the infection and its endemicity. These challenges put pregnant women, young children and children with disabilities at especially high risk for contracting Chagas disease. Left untreated, Chagas disease can lead to serious heart, digestive and neurological conditions.

scholarly journals First-Time Mothers Have a Desire to Be Offered Professional Breastfeeding Support by Pediatric Nurses: An Evaluation of the Mother-Perceived-Professional Support Scale

2019 ◽  
Vol 2019 ◽  
pp. 1-11 ◽  
Author(s):  
Matilda Möller Ranch ◽  
Sofia Jämtén ◽  
Stina Thorstensson ◽  
Anette C. Ekström-Bergström
Keyword(s):  
Qualitative Content Analysis ◽  
Professional Support ◽  
World Health ◽  
Perceived Support ◽  
Pediatric Nurses ◽  
Breastfeeding Support ◽  
Semistructured Interviews ◽  
First Time Mothers ◽  
Health Organization ◽  
First Time

Background. Although the World Health Organization recommends exclusive breastfeeding for six months, the rate of breastfeeding has decreased worldwide. Breastfeeding is the natural way of feeding a baby, but it is a process that has to be learnt. It is not unusual for problems to occur and hence support for breastfeeding is vital. The aim of this study was to explore first-time mothers’ experiences of the breastfeeding support offered by pediatric nurses, as well as to develop and evaluate the Mother Perceived Support from Professionals (MoPPS) scale. Methods. A qualitative design involving both inductive and deductive approaches was chosen. Nine first-time mothers were interviewed regarding their experiences of the breastfeeding support offered by pediatric nurses. Semistructured interviews were conducted. The mothers were also asked to grade their experiences of breastfeeding support on the MoPPS scale. A qualitative content analysis was applied when analyzing the data obtained using both the inductive (interviews) and deductive (MoPPS scale) approaches. Results. The results revealed that the mothers felt the desire to breastfeed, although they all experienced some difficulties. They wanted the pediatric nurses to be perceptive and provide professional support based on their own experiences. When the pediatric nurses took time and booked extra appointments, the mothers felt supported. The inductive analysis resulted in one theme: “When wanting to breastfeed, mothers have a desire to be offered professional breastfeeding support”. Two main categories were identified, namely “Mothers wanted but lacked breastfeeding support” and “Mothers received professional support.” The deductive analysis of the MoPPS scale showed similar results, and the questions were perceived as relevant to the aim. The mothers considered it important that the pediatric nurses had sufficient knowledge about breastfeeding. It was also considered important that the pediatric nurses involved the mothers’ partners in the breastfeeding support. Therefore, we suggest that these areas should be included in the MoPPS scale for pediatric nurses. Conclusions. The MoPPS scale can be a useful tool for helping pediatric nurses to offer mothers professional breastfeeding support. Indeed, when offering breastfeeding support, pediatric nurses can use the items included on the MoPPS scale as guidance.

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