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1.
Arch. cardiol. Méx ; 92(3): 342-348, jul.-sep. 2022. tab, graf
Article in Spanish | LILACS-Express | LILACS | ID: biblio-1393829

ABSTRACT

Resumen Objetivos: Determinar si los pacientes con cardiopatía chagásica (CCh) presentaron choques apropiados del desfibrilador automático implantable (DAI) de manera más precoz que los pacientes con cardiopatía isquémica (CI). Métodos: Estudio de cohorte retrospectivo que incluyó los pacientes con CCh y CI en quienes se implantó un DAI entre los años 2009 y 2018 en un hospital de alta complejidad. El seguimiento se realizó hasta los 36 meses, evaluándose el momento del primer choque apropiado del dispositivo. Resultados: Se incluyeron 64 pacientes, 20 con CCh y 44 con CI. Se observó que una mayor proporción de pacientes con CCh presentaron choques apropiados durante el primer año (hazard ratio [HR]: 8.4; intervalo de confianza del 95% [IC95%]: 2.09-34.02; p = 0.0027) y a 3 años (HR: 4.61; IC95%: 1.51-14.07; p = 0.0072). El 100% de la población con CCh e implante del DAI como prevención secundaria de muerte súbita presentaron choques apropiados durante los primeros 26 meses de seguimiento. Conclusiones: Los pacientes con CCh presentaron choques apropiados del DAI de manera más precoz que los pacientes con CI. Todos los pacientes con CCh y DAI como prevención secundaria presentaron choques apropiados, representando una población de mayor riesgo. Esta información apoya la indicación del DAI en estos pacientes a pesar de la escasa evidencia en ensayos aleatorizados.


Abstract Objetives: To assess if patients with Chagasic heart disease (CHD) received effective automatic implantable defibrillator (AID) shocks earlier than patients with ischemic heart disease (IHD). Methods: Retrospective cohort of patients with CHD and IHD who received an implantable cardioverter defibrillator (ICD) between 2009 and 2018, in a tertiary hospital. We evaluated the time between the implant of ICD and the first effective shock in patients with CHD and compared it with the IHD control population. Results: We included a total of 64 patients, 20 with CHD and 44 with IHD. CHD patients presented earlier an effective shock than patients with IHD during the first year (hazard ratio [HR]: 8.4; 95% confidence interval [95% CI]: 2.09-34.02; p = 0.0027), and at three years (HR: 4.61; 95% CI: 1.51-14.07; p = 0.0072). 100% of CHD patients who received the ICD as secondary prevention of sudden cardiac death presented an effective shock during the first 26 months of follow-up. Conclusions: Patients with CHD received effective ICD shocks earlier than the IHD patients. All patients with CHD and ICD as secondary prevention had an appropriate ICD shock at short term, representing the highest risk population, and supporting the indication of the device in a setting where randomized clinical trials are lacking.

2.
Rev. bras. cir. cardiovasc ; 37(4): 423-429, Jul.-Aug. 2022. tab
Article in English | LILACS-Express | LILACS | ID: biblio-1394739

ABSTRACT

ABSTRACT Introduction: Implantable cardiac pacemakers or cardioverter defibrillators are alternatives for the treatment of arrhythmias, however, their use has caused changes in the emotional state of patients. The objective of this study was to compare the measures of anxiety and depression symptoms in individuals according to their sex, type of cardiac device, and diagnosis of Chagas disease. Methods: This is an observational and cross-sectional study conducted with adults with implantable cardiac pacemakers or cardioverter defibrillators. Data was collected using a sociodemographic and clinical questionnaire and the Hospital Anxiety and Depression Scale. We used the Student's t-test for independent samples and the Chi-squared test, with a significance level of 0.05. Results: Two hundred forty-four patients participated in the study, 168 with cardiac pacemakers and 76 with implantable cardioverter defibrillators; 104 had Chagas cardiomyopathy (85 with cardiac pacemakers and 19 with implantable cardioverter defibrillators). No statistically significant differences were found in measures of anxiety and depression symptoms according to device type (P=0.594 and P=0.071, respectively) and the presence of Chagas etiology (P=0.649 and P=0.354, respectively). Women had higher mean scores for anxiety (P=0.002) and depression symptoms (P<0.001). Conclusion: In the comparison between the groups, according to the type of implanted device and the diagnosis of Chagas disease, no significant differences were found in the measures of anxiety and depression symptoms. Women showed higher means when compared to men, indicating the need to test and implement interventions to minimize these symptoms in this population.

3.
Arq. gastroenterol ; 59(2): 281-287, Apr.-June 2022. tab
Article in English | LILACS-Express | LILACS | ID: biblio-1383837

ABSTRACT

ABSTRACT Background: No study has focused on Health-Related Quality of Life (HRQoL) for Chagas Achalasia patients. Objective: To compare HRQoL between Chagas Achalasia patients and the general population; and to correlate HRQoL with clinical factors that can affect it. Methods: Sixty Chagas Achalasia patients and 50 controls were evaluated. All patients underwent esophageal manometry for the diagnosis of achalasia and esophagogram to determine the grade of megaesophagus. Three questionnaires were used: 1) clinical: the following data were collected: demographic, medical history, body mass index, occurrence of six esophageal symptoms (Esophageal Symptom Score: number of symptoms reported by patients), duration of dysphagia; 2) socio-economic-cultural status evaluation: patients and controls answered seven questions about their socio-economic-cultural conditions; 3) HRQoL: the validated Brazilian-Portuguese version of the Short-form Health Survey (SF-36) questionnaire (license QM020039) was used. It measures health in eight domains: 3a) four physical: physical functioning, role limitations relating to physical health, bodily pain, and general health perception; 3b) four mental: vitality, social functioning, role limitations relating to emotional health, and mental health. These domains can be summarized into Physical and Mental Summary scores. We analyzed correlations between SF-36 Physical/Mental Summary Component scores and the following clinical factors: Esophageal Symptom Score, duration of dysphagia, body mass index, grades of megaesophagus (defined by the esophagogram) and presence/absence of megacolon (defined by opaque enema). Results: Patients and controls had similar age, gender, medical history, and socio-economic-cultural lifestyles (P>0.05). All patients had dysphagia and megaesophagus. SF-36 scores were significantly lower in Chagas Achalasia patients than controls for all eight domains (physicals: P<0.002; mentals: P<0.0027). The Physical and Mental Summary Component scores were also lower in Chagas Achalasia patients than controls (P<0.0062). For patients, the Physical Summary score was negatively correlated to Esophageal Symptom Score (P=0.0011) and positively correlated to body mass index (P=0.02). No other correlations were found. Conclusion: Chagas Achalasia patients have an impaired HRQoL in all physical and mental domains. Patients reporting more symptoms had worse physical domains. Patients with higher body mass index had better physical domains.


RESUMO Contexto: Não encontramos na literatura estudos sobre a qualidade de vida em pacientes com acalásia chagásica especificamente. Objetivo: Comparar a qualidade de vida de pacientes com acalásia chagásica e a da população em geral. Também, correlacionar a qualidade de vida nestes pacientes com fatores clínicos que possam afetá-la. Métodos: Estudamos 60 pacientes com acalásia chagásica e 50 controles. Todos os pacientes foram submetidos à manometria esofágica para diagnóstico de acalásia e esofagograma técnica padrão para determinar o grau do megaesôfago. Usamos 3 questionários: 1) clínico: foram coletados os seguintes dados: demográficos, história clínica, índice de massa corporal, presença de seis sintomas esofágicos (definimos Escore de Sintomas Esofágicos como o número de sintomas relatados pelos pacientes), duração da disfagia; 2) avaliação sócio-econômico-cultural: sete questões sobre as condições sócio-econômico-culturais foram perguntadas para pacientes e controles; 3) qualidade de vida: foi avaliada pelo questionário SF-36, versão validada para o português-Brasil (licença QM020039). Este é um questionário genérico que mede a qualidade de vida em oito domínios: 3a) quatro físicos: capacidade funcional, aspectos físicos, dor corporal, estado geral de saúde; 3b) quatro mentais: vitalidade, aspectos sociais, aspectos emocionais, saúde mental. Estes oito domínios podem ser compilados em dois escores: Sumário dos Escores Físicos e Sumário dos Escores Mentais. Na análise de fatores clínicos que pudessem afetar a qualidade de vida dos pacientes, avaliamos: escores de sintomas esofágicos, duração da disfagia, índice de massa corporal, graus de megaesôfago e presença/ausência de megacólon. Resultados: Os dois grupos (pacientes e controles) apresentaram semelhantes idade, gênero, história médica e condições socioeconômico-culturais (P>0,05). Todos os pacientes tinham disfagia e megaesôfago. Com relação à qualidade de vida, pacientes com acalásia chagásica apresentaram valores significativamente menores do que os controles em todos os domínios do questionário SF-36 (domínios físicos: P<0,002; domínios mentais: P<0,0027). Os Sumários dos Escores Físicos e Mentais também foram significativamente menores em pacientes do que nos controles (P<0.0062). A análise dos fatores clínicos que poderiam afetar a qualidade de vida nos pacientes mostrou que o Sumário dos Escores Físicos se correlaciona negativamente com o Escores Dos Sintomas Esofágicos (P=0,0011) e positivamente com o índice de massa corporal (P=0,02). Não observamos qualquer outra correlação. Conclusão: Pacientes com Acalásia Chagásica têm pior qualidade de vida que a população em geral, em todos os domínios físicos e mentais. Pacientes que relataram mais sintomas apresentaram pior qualidade de vida nos domínios físicos. Pacientes com valores maiores de índice de massa corporal apresentaram melhor qualidade de vida nos domínios físicos.

4.
Int. j. cardiovasc. sci. (Impr.) ; 35(3): 354-363, May-June 2022. tab, graf
Article in English | LILACS | ID: biblio-1375637

ABSTRACT

Abstract Background: Different immune mechanisms of myocardial damage involved in the pathophysiology of Chagas disease coexist with high titers of autoantibodies induced by T. cruzi . There are few studies in the literature about the adaptive role of anti-β1 and anti-M2 antibodies in chronic Chagas cardiomyopathy (CCC). Objectives: To evaluate the association between anti-β1 and anti-M2 antibodies with heart rate variability (HRV) parameters on 24h Holter monitoring and the rate-pressure product (RPP) on cardiopulmonary exercise testing (CPET). Methods: Anti-β1 and anti-M2 antibody titers were measured by enzyme-linked immunosorbent assay (ELISA) in 64 patients affected by CCC. Analysis of HRV was performed through the time-domain indices NNs, mean NN, SDNN, SDANN, SDNN index, NNNs, RMSSD, and pNN50. Spearman's correlation coefficient was used to assess the association between antibody titers and numerical variables. The Mann-Whitney test was used for comparison between two groups. Multiple linear regression was used to identify independent variables capable of explaining anti-β1 and anti-M2 antibody titers at the 5% significance level. Results: On 24h Holter, during the period of greatest parasympathetic activation (2:00-6:00 a.m.), an inverse association was found between anti-β1 titers and SDNN (rs=-0.13, p =0.041, n=43), as well as a direct association between anti-M2 titers and SDANN ( r s=0.317, p =0.039, n=43). Regarding CPET variables, anti-β1 titers were directly associated with RPP (rs=0.371, p =0.005, n=56). The subgroup of patients with a normal chronotropic response showed higher anti-β1 titers than the subgroup with an impaired response (p=0.023). RPP was an independent explanatory variable for anti-β1 titers, although with a low coefficient of determination (R2=0.147). Conclusion: The findings of this study suggest that, in patients with CCC, anti-β1 and anti-M2 antibodies may affect HRV parameters. RPP was directly associated with higher anti-β1 titers.


Subject(s)
Humans , Male , Female , Adult , Middle Aged , Aged , Aged, 80 and over , Young Adult , Autonomic Nervous System/physiology , Chagas Cardiomyopathy/physiopathology , Receptors, Adrenergic, beta-1/physiology , Receptor, Muscarinic M2/physiology , Chronic Disease , Cross-Sectional Studies , Antibodies, Bispecific , Exercise Test
6.
Ciênc. Saúde Colet. (Impr.) ; 27(5): 1939-1949, maio 2022. graf
Article in Portuguese | LILACS-Express | LILACS | ID: biblio-1374956

ABSTRACT

Resumo O artigo tem por objetivo analisar as histórias de vida de portadores de doença de Chagas (DC), para evidenciar em suas narrativas elementos e possibilidades de enfrentamento dessa problemática. Causada pelo protozoário Trypanosoma cruzi, a DC combina condições de infecção assintomática e/ou de progressão para doença de acordo com determinantes biológicos e sociais e afeta 6 a 7 milhões de pessoas infectadas. No mundo anualmente 6 mil pessoas em consequência das complicações na fase crônica da DC. Realizamos um estudo qualitativo com uso da técnica de história de vida coletadas em entrevistas abertas, coletando um material riquíssimo para trabalhar o contexto da doença em múltiplas dimensões. Associamos uma escuta sensível com a necessidade das pessoas vivendo com a DC darem força à sua voz, valorizando sua própria história de vida, transformando-as em detendoras de sua história e de seu conhecimento. A visibilidade emergiu e prevaleceu, expondo a própria doença como tema central e dois subtemas gerais: suas percepções sobre a doença e a sua própria vida, no contexto da doença. Identificamos a necessidade de (re)pensar a problemática da doença de Chagas como algo visível e presente.


Abstract The scope of this article is to analyze the life histories of Chagas disease (CD) patients, searching for elements in their narratives that might present possibilities for coping with this problem. Caused by the protozoan Trypanosoma cruzi, Chagas disease combines conditions of infection and/or progression to disease, in accordance with biological and social determinants and affects around 6 to 7 million people infected with T. cruzi. More than 6,000 people die each year due to complications in the chronic CD phase. This is a qualitative study using the life history technique that was used in open interviews. We collected a wealth of material with which we can work on the context of the disease in multiple dimensions. We associate sensitive listening with the needs of people living with the CD to give strength to their voice, valuing their own life story, transforming them into masters of their history and knowledge. Visibility emerged and prevailed, exposing the disease itself as a central theme and two general sub-themes: their perceptions about the disease and their own life, in the context of the disease. We identified the need to (re)think the problem of Chagas disease as something visible and present.

7.
Rev. bras. cir. cardiovasc ; 37(2): 263-267, Apr. 2022. tab, graf
Article in English | LILACS-Express | LILACS | ID: biblio-1376529

ABSTRACT

ABSTRACT Introduction: Combined solid organ transplantation is infrequently performed in Brazil. The objective of this article is to present our initial experience with combined heart and kidney transplantation. Methods: From January 2007 to December 2019, four patients were submitted to combined heart and kidney transplantation. Their mean age was 55.7±4.4 years, and three (75%) patients were males. All patients had Chagas cardiomyopathy, two were hospitalized and inotrope dependent, and all patients were on preoperative dialysis (median of 12 months prior to transplant). Results: All patients survived and were in New York Heart Association functional class I at the latest follow-up (mean 34.7±17.5 months). Mean retarded kidney graft function was 22.9±9.7 days. One patient lost the kidney graft two years after the transplant due to Polyomavirus infection. Conclusion: Our initial experience of combined heart and kidney transplantation was favorable in selected patients with advanced heart failure and end-stage kidney disease. It requires involvement of a dedicated multispecialty team throughout all the diagnostics and treatment steps.

9.
Int. j. cardiovasc. sci. (Impr.) ; 35(2): 267-282, Mar.-Apr. 2022. graf
Article in English | LILACS | ID: biblio-1364971

ABSTRACT

Abstract In 1907, Carlos Chagas was designated to fight paludism in the Rio das Velhas region along the Central do Brasil railroad. During his field research, Chagas discovered a hematophagous insect ( Panstrongylus megitus ) carrying a new trypanosomatide, which he named Trypanosoma cruzi . On April 14th, 1909, he found the same parasite in the blood of a febrile child, submitting the announcement of his discoveries to the Brasil Médico scientific journal. Here, we discuss the early stages in the establishment of a new human morbid entity during the first decades after its discovery with a definite influence from its discoverer, Carlos Chagas, as well the first collaborators. Moreover, we cover the importance of the Center for the Study and Prophylaxis of Chagas Disease in Bambuí (MG), unraveling the most advanced developments in research within the disease's habitat and the widening perspectives for modern research that have emerged after the 1960s and continue to improve to this day. In this revisitation to the history of Chagas disease, we begin at Manguinhos (RJ ), making our way to Lassance (MG), where the discovery took place. Then, we travel back to Rio de Janeiro in the beginning of the twentieth century and Brazilian republic until the current day, revealing milestone publications that settled Chagas disease both as a source of pride for Brazilian medicine and as a challenge with important aspects that remain to be clarified. Any similarities to our country's politics and economy in the twentieth century are not mere coincidences.


Subject(s)
Humans , Chagas Disease/etiology , Chagas Disease/history , Trypanosoma cruzi , Chagas Cardiomyopathy/etiology , Chagas Cardiomyopathy/history
10.
Ciênc. Saúde Colet. (Impr.) ; 27(3): 871-879, mar. 2022.
Article in Spanish | LILACS | ID: biblio-1364690

ABSTRACT

Resumen A través de una etnografía basada en la observación, entrevistas a profesionales y el vaciado de documentación, en este artículo describo y analizo cómo, en la práctica clínica del Chagas, la infección es tratada como un riesgo latente. Sugiero que la gestión que se hace de este riesgo ha posibilitado la práctica clínica entre las personas clasificadas en la etapa indeterminada, añadiendo una dimensión de posibilidad (¿va a pasar?) y de potencialidad (¿cuándo y dónde?) que permite tomar acciones tales como la administración de un medicamento o una monitorización permanente. La reificación del riesgo latente como fenómeno gestionable a través de un proceso de medicalización se articula, a su vez, con otras concepciones y experiencias concretas del riesgo entre los grupos afectados. Situar la práctica clínica de dicho riesgo como objeto de estudio es un primer paso para poderlas describir e incluir como realidades en la organización del sistema de salud.


Abstract Drawing on observation-based ethnography, interviews of health personnel and document review, this article describes and examines how, in clinical handling of Chagas disease, infection is treated as latent risk. It suggests that how this risk is managed has enabled a clinical practice to be conducted among people classified as at the indeterminate stage, by adding a dimension of possibility (Is it going to happen?) and potentiality (When and where?). This allows measures to be taken, including administration of medication or permanent monitoring. The reification of latent risk as a phenomenon that is manageable through a process of medicalisation engages, in turn, with other conceptions and specific experiences of risk among the affected groups. Framing the clinical practices deployed to address this risk as objects of study is a first step towards being able to describe and include them concretely in health system organisation.


Subject(s)
Humans , Anthropology, Cultural
11.
Mem. Inst. Oswaldo Cruz ; 117: e210395, 2022.
Article in English | LILACS-Express | LILACS | ID: biblio-1360602

ABSTRACT

Transforming growth factor beta (TGF-β) is deeply involved on the pathogenesis of Chagas disease. Our group has been investigating the participation of this pleiotropic cytokine in different aspects of Chagas disease over the last 20 years. Important observations have been made, such as: (i) the ability of Trypanosoma cruzi in activating latent TGF-β; (ii) the potential involvement of TGF-β pathway on T. cruzi invasion of host cells; (iii) association of TGF-β with parasite intracellular replication; (iv) cardiac fibrosis development and maintenance; (v) disruption of Connexin-43 plaque structures and (vi) inflammation and immune response. In this perspective article we intend to discuss the advances of the potential use of new therapies targeting TGF-β to treat the cardiac alterations of Chagas disease-affected patients.

12.
Article in English | LILACS-Express | LILACS | ID: biblio-1360790

ABSTRACT

ABSTRACT The present study aimed to establish a population pharmacokinetic (PopPK) modeling of benznidazole (BZD) in Brazilian patients with chronic Chagas disease. This was part of a Brazilian prospective cohort study with eight patients diagnosed with Chagas disease during the beginning of BZD treatment up to the 60th day. On the 15th day of treatment, a blood sampling was collected and analyzed. A one-compartment PK model was developed using Pmetrics. Patients with an average age of 50.3 (SD: 6.2) years old, 6 female patients and 2 males, 70.2 kg (14.2), receiving a 5 mg/Kg/day dose were included. PK parameters estimated for CL, V and Ka were 6.27 L/h, 38.97 L and 1.66 h-1, respectively. This is the first study to establish a population pharmacokinetic modeling of BZD in Brazilian patients with chronic Chagas disease. Therefore, further studies are needed to obtain the complete characterization of BZD pharmacokinetics.

13.
Article in English | LILACS-Express | LILACS | ID: biblio-1360793

ABSTRACT

ABSTRACT Chagas disease is among the 21 neglected diseases according to the World Health Organization. This study aimed to investigate the morbidity and mortality distribution of Chagas disease for identifying areas with greater prevalences and deaths of the disease in Northeast Brazil. A population-based ecological study was performed from 2016 to 2018 using data on acute Chagas disease patients from the Disease Notification Information System, chronic cases from the Chagas Disease and the referral Heart Failure Outpatient Clinic in Pernambuco, and Chagas disease-related mortality from the Mortality Information System. The unit of analysis were Pernambuco State mesoregions. The indicators were spatialized into thematic maps on the occurrence and mortality of the disease per 100,000 inhabitants. No cases of acute disease were reported in the period analyzed. Data on 801 chronic Chagas disease patients were analyzed. The population showed an average age of 62 years, with female predominance. The most prevalent comorbidity was systemic arterial hypertension and cardiologic involvement without ventricular dysfunction. The average chronic disease occurrence rate was 3.2/ 100,000 people/ year. As for deaths in the mortality system; in total, 350 deaths were recorded, showing male predominance, age ≥ 60 years, and chronic disease with cardiac involvement as the main mortality cause. The annual average mortality proportion was 1.6/100,000 people. The chronic case distribution showed spatial heterogeneity, with the highest rates of chronic disease and deaths observed in two mesoregions, with the main cause of death being heart-related. This highlights the need for more specialized services in areas with higher burden of the disease to avoid delay in the patients' care.

14.
Rev. Soc. Bras. Med. Trop ; 55: e0553, 2022. tab
Article in English | LILACS-Express | LILACS | ID: biblio-1360812

ABSTRACT

ABSTRACT Background: Chagas disease (CD) is caused by the flagellate protozoan Trypanosoma cruzi and can be carried by different species of triatomines, including Rhodnius neglectus, which is wild, well distributed in Brazil, and has formed colonies in palm trees located in urban areas of municipalities in the state of São Paulo. Chemical control has been routinely used to reduce population density, but each year, there has been an increase in species dispersion and density. This study aimed to evaluate the susceptibility of insects to insecticides used in control. Methods: The reference population was collected from Araçatuba municipality, Nilce Maia. Dilutions of deltamethrin were prepared and applied to the back of the first-stage nymphs, which were biologically synchronized. The control group received pure acetone only. Mortality was assessed after 72 h. Results: The mortality rate with respect to diagnostic dose was 100%. The susceptibility profile observed for this population showed RR50 ranging from 1.76 to 3.632. Conclusions: The populations were susceptible to the insecticides tested. It is possible that the insecticide residual effect on this ecotope has decreased the lifespan, and controlling failures may be the cause of recolonization in this environment.

15.
Rev. Soc. Bras. Med. Trop ; 55: e0562, 2022. tab
Article in English | LILACS-Express | LILACS | ID: biblio-1360819

ABSTRACT

ABSTRACT Background We investigated the mortality rates of patients with Chagas disease (CD) during the coronavirus disease 2019 (COVID-19) pandemic and assessed the association between this mortality and CD clinical presentation and comorbidities. Methods: This was an observational retrospective study with clinical data retrieved from medical records. Results: Comorbidities were more prevalent among patients who died from COVID-19 than those who died from other causes. The proportion of patients according to CD clinical presentation was similar between the two groups. Conclusions: The prevalence of comorbidities seems to be related to a poorer prognosis in CD and COVID-19.

16.
Mem. Inst. Oswaldo Cruz ; 117: e210385, 2022. tab, graf
Article in English | LILACS-Express | LILACS | ID: biblio-1365149

ABSTRACT

The need to develop safer and more efficacious drugs to treat Chagas disease has motivated the search for cruzain inhibitors. Cruzain is the recombinant, truncated version of cruzipain, a cysteine protease from Trypanosoma cruzi with important roles during the parasite life cycle. Several computational techniques have been applied to discover and optimise cruzain inhibitors, providing a molecular basis to guide this process. Here, we review some of the most recent computational studies that provided important information for the design of cruzain inhibitors. Moreover, we highlight the diversity of applications of in silico techniques and their impact.

17.
Mem. Inst. Oswaldo Cruz ; 117: e220004, 2022.
Article in English | LILACS-Express | LILACS | ID: biblio-1365152

ABSTRACT

Chagas disease (CD), a neglected tropical illness caused by the protozoan Trypanosoma cruzi, affects more than 6 million people mostly in poor areas of Latin America. CD has two phases: an acute, short phase mainly oligosymptomatic followed to the chronic phase, a long-lasting stage that may trigger cardiac and/or digestive disorders and death. Only two old drugs are available and both present low efficacy in the chronic stage, display side effects and are inactive against parasite strains naturally resistant to these nitroderivatives. These shortcomings justify the search for novel therapeutic options considering the target product profile for CD that will be presently reviewed besides briefly revisiting the data on phosphodiesterase inhibitors upon T. cruzi.

18.
Mem. Inst. Oswaldo Cruz ; 117: e220019, 2022. graf
Article in English | LILACS-Express | LILACS | ID: biblio-1365154

ABSTRACT

Chagas disease (CD), caused by infection by the protozoan parasite Trypanosoma cruzi, presents as main clinical manifestation the chronic chagasic cardiomyopathy (CCC). CCC afflicts millions of people, mostly in Latin America, and vaccine and effective therapy are still lacking. Comprehension of the host/parasite interplay in the chronic phase of T. cruzi infection may unveil targets for rational trait-based therapies to improve CCC prognosis. In the present viewpoint, I critically summarise a collection of data, obtained by our network of collaborators and other groups on CCC and preclinical studies on pathogenesis, targeting identification for intervention and the use of drugs with immunomodulatory properties to improve CCC. In the last two decades, models combining mouse lineages and T. cruzi strains allowed replication of crucial clinical, histopathological, and immunological traits of CCC. This condition includes conduction changes (heart rate changes, arrhythmias, atrioventricular blocks, prolongation of the QRS complex and PR and corrected QT intervals), ventricular dysfunction and heart failure, CD8-enriched myocarditis, tissue remodeling and progressive fibrosis, and systemic inflammatory profile, resembling "cytokine storm". Studies on Chagas' heart disease pathogenesis begins to unveil the molecular mechanisms underpinning the inflammation-related cardiac tissue damage, placing IFNγ, TNF and NFκB signaling as upstream regulators of miRNAs and mRNAs associated with critical biological pathways as cell migration, inflammation, tissue remodeling and fibrosis, and mitochondrial dysfunction. Further, data on preclinical trials using hypothesis-based tools, targeting parasite and inflammation-related alterations, opened paths for multi-therapeutic approaches in CCC. Despite the long path taken using experimental CD models replicating relevant aspects of CCC and testing new therapies and therapeutic schemes, these findings may get lost in translation, as conceptual and economical challenges, underpinning the valley of death across preclinical and clinical trials. It is hoped that such difficulties will be overcome in the near future.

19.
Mem. Inst. Oswaldo Cruz ; 117: e220017, 2022. graf
Article in English | LILACS-Express | LILACS | ID: biblio-1365156

ABSTRACT

The treatment for tropical neglected diseases, such as Chagas disease (CD) and leishmaniasis, is extremely limited to a handful of drugs that suffer from unacceptable toxicity, tough administration routes, like parenteral, and increasing treatment failures due to the parasite resistance. Consequently, there is urgency for the development of new therapeutic options to treat such diseases. Since peptidases from these parasites are responsible for crucial functions in their biology, these molecules have been explored as alternative targets. In this context, a myriad of proteolytic inhibitors has been developed against calcium-dependent cysteine-type peptidases, collectively called calpains, which are implicated in several human pathophysiological diseases. These molecules are highly expanded in the genome of trypanosomatids and they have been reported participating in several parasite biological processes. In the present perspective, we discuss our almost two decades of experience employing the calpain inhibitors as an interesting shortcut to a possible repurpose strategy to treat CD and leishmaniasis.

20.
Rev. Soc. Bras. Med. Trop ; 55: e0657, 2022. tab, graf
Article in English | LILACS-Express | LILACS | ID: biblio-1365438

ABSTRACT

ABSTRACT Chagas disease (CD) is a neglected tropical disease associated with poverty in which patients are surrounded by stigma. These factors can contribute to reducing health-related quality of life (HRQoL). Therefore, a broad discussion of HRQoL in the CD population is required. This study aimed to discuss the main findings of HRQoL in patients with CD, focusing on the association between sociodemographic and lifestyle factors, echocardiographic and functional determinants, and the effect of non-invasive interventions on HRQoL. A literature search of the MEDLINE, Web of Science, CINAHL, Scopus, and LILACS databases was performed with no data or language restrictions. Twenty-two articles were included in this meta-analysis. In general, HRQoL is worse in patients with CD than in healthy individuals, particularly in the presence of cardiovascular and/or gastrointestinal symptoms. Sex, age, functional class, level of physical activity, healthy habits, and medications received could affect HRQoL. Among the echocardiographic and functional determinants, decreased systolic function seems to negatively affect HRQoL. No association with the peak oxygen uptake was observed in the maximal tests. By contrast, well-tolerated field tests with submaximal intensities were associated with HRQoL. Both pharmaceutical care and exercise training have a positive effect on the HRQoL of patients with Chagas cardiomyopathy, and the mental component can be a prognostic marker in this population. In conclusion, assessment of HRQoL can provide important information about the health status of patients with CD, and its use in clinical practice is warranted.

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