Plasma Lysophosphatidylcholine and Phospholipase A2 Activity in Chagas Disease Patients: A Comparative Analysis

Chagas disease (CD) affects 21 countries in the Americas and is caused by the parasite Trypanosoma cruzi. A key molecule involved in CD is lysophosphatidylcholine (LPC), which has been studied in various contexts: in the saliva of insect vectors, during the establishment of infection in the vertebrate host, and for the parasite itself. This lipid can be produced by the action of phospholipases A2 (PLA2), enzymes that catalyze the hydrolysis of phospholipids releasing fatty acids and lysophospholipids, such as LPC. This study investigates LPC levels and PLA2 activities in the plasma of CD patients and compares these levels with those in healthy individuals and patients with idiopathic dilated cardiomyopathy (IDCM). Plasma from 64 CD patients, 54 healthy individuals, and 16 IDCM patients were analyzed. LPC levels and the activity of two types of phospholipase A2: secreted (sPLA2) and lipoprotein-associated (Lp-PLA2) were measured. LPC levels and sPLA2 activity were similar between CD patients and the control groups. However, there were notable differences in LPC levels and sPLA2 activity between subgroups of CD patients and IDCM patients. This study is the first to identify LPC in patients with CD across various stages of the disease. It also offers new insights into the biochemical changes observed in the plasma of patients with IDCM.

Evaluation of parasitemia by qPCR in patients with chronic Chagas disease treated with benznidazole

Objective:To evaluate parasitemia by qPCR in patients undergoing etiological treatment and followed in a Brazilian reference center.Methods:Parasite load was quantified by qPCR in 32 participants with chronic Chagas disease who were treated with benznidazole.Serological analyses were performed before and after the treatment and parasite loads were compared prior and 12/18 months post the treatment.Results:Thirty-two participants were recruited and treated with benznidazole,and 20 were followed-up.Adverse events(AE)were observed in 22 out of 29 participants that had safety data(76%),and dermatological alterations were the most frequently observed AE.Of the 20 participants analyzed,13 and 7 completed 12 and 18 months follow-up after the treatment,respectively.12 Months after the final treatment,Trypanosoma cruzi was detectable in 3 patients by qPCR;18 months after the final treatment,Trypanosoma cruzi was detectable per qPCR in 4 of the 7 participants.Thus,between 12 and 18 months,7 participants of the 20 initial follow-up cases showed positive qPCR,indicating treatment failures.Conclusions:qPCR can be used as an alternative method for evaluating the effectiveness of the etiological treatment of CD,and can be applied to analyze early therapeutic failures.The study showed that benznidazole therapy had limited effectiveness in treating chronic CD patients,thus emphasizing the importance of conducting continued research for developing more effective therapies and diagnosis for CD.

Chagas心脏病研究现状

Chagas病即查加斯病,是一个古老的热带寄生虫病。该病由克氏锥虫感染引起,可累及皮肤、心脏和消化道等全身多个系统,因其广泛流行于墨西哥及拉丁美洲国家的贫穷地区也被称为美洲锥虫病（American trypanosomiasis）。

画高原艺韵 探传承篇章——访著名藏族美术研究学者根秋登子

根秋登子教授,曾任四川省藏文学校副校长、甘孜州藏学研究所所长、编译中心主任及甘孜州政协副主席等职。2006年作为引进人才到西南民族大学任教授,2016年作为外聘专家到四川大学喜马拉雅研究中心工作。现任国家“十三五”重点规划项目“西藏特色文化资源库建设”专家委员会主任、中国唐卡艺术专业委员会副主任。先生主要从事藏族美术创作与研究工作,先后出版专著20余种;发表藏、汉文学术论文(散文)100余篇;在美国哥伦比亚大学、德国汉堡大学等国内外知名院校和学术机构讲座120余次。文章围绕根秋登子先生的学术经历、成就及贡献等对其进行了专访。

Clinicopathological alterations in wild mammals from the reservoir system of Trypanosoma cruzi:a scoping review

Trypanosoma cruzi is the etiologic agent of Chagas disease.This flagellated protozoan is transmitted to humans as well as different species of domestic and wild animals via vectors from the Reduviidae family(known as"kissing bugs").Despite the fact that hundreds of species of wild mammals are part of the reservoir system,the morphologi-cal changes and clinical manifestations resulting from the pathogenesis of the infection have been largely neglected.The aim of this review is to systematically compile the available information regarding clinicopathological altera-tions in wild mammals due to natural infection by T.cruzi.Information was obtained from six online bibliographic data search platforms,resulting in the identification of 29 publications that met the inclusion criteria.Mortality was the most common clinical manifestation,cardiac damage was the main finding at necropsy,and lymphoplas-macytic inflammation was the most frequent microscopic injury.Thus,regardless of its role as a reservoir,T.cruzi has the potential to affect the health status of wild mammals,a situation that highlights the need for further research to analyze,measure,and compare its effects at both the individual and population levels.

Chagas氏病的诊断:重组ELISA与传统ELISA和血凝反应实验的比较分析

背景和目的 南美血库Chagas氏病(南美锥虫病)血清学筛查是通过两种不同的检测方法进行的,这两种方法往往会有大量不确定的结果。解决这一难题,作者比较了重组ELISA法和这两种传统方法。材料与方法 分别用重组EIJISA(Re-

Modulation of immune response in experimental Chagas disease

Trypanosoma cruzi(T. cruzi), the etiological agent of Chagas disease, affects nearly 18 million people in Latin America and 90 million are at risk of infection. The parasite presents two stages of medical importance in the host, the amastigote, intracellular replicating form, and the extracellular trypomastigote, the infective form. Thus infection by T. cruzi induces a complex immune response that involves effectors and regulatory mechanisms. That is why control of the infection requires a strong humoral and cellular immune response; hence, the outcome of host-parasite interaction in the early stages of infection is extremely important. A critical event during this period of the infection is innate immune response, in which the macrophage's role is vital. Thus, after being phagocytized, the parasite is able to develop intracellularly; however, during later periods, these cells induce its elimination by means of toxic metabolites. In turn, as the infection progresses, adaptive immune response mechanisms are triggered through the TH1 and TH2 responses. Finally, T. cruzi, like other protozoa such as Leishmania and Toxoplasma, have numerous evasive mechanisms to the immune response that make it possible to spread around the host. In our Laboratory we have developed a vaccination model in mice with Trypanosoma rangeli, nonpathogenic to humans, which modulates the immune response to infection by T. cruzi, thus protecting them. Vaccinated animals showed an important innate response(modulation of NO and other metabolites, cytokines, activation of macrophages), a strong adaptive cellular response and significant increase in specific antibodies. The modulation caused early elimination of the parasites, low parasitaemia, the absence of histological lesions and high survival rates. Even though progress has been made in the knowledge of some of these mechanisms, new studies must be conducted which could target further prophylactic and therapeutic trials against T. cruzi infection.

Preclinical stem cell therapy in Chagas Disease: Perspectives for future research

Chagas cardiomyopathy still remains a challenging problem that is responsible for high morbidity and mortality in Central and Latin America. Chagas disease disrupts blood microcirculation via various autoimmune mechanisms, causing loss of cardiomyocytes and severe impairment of heart function. Different cell types and delivery approaches in Chagas Disease have been studied in both preclinical models and clinical trials. The main objective of this article is to clarify the reasons why the benefits that have been seen with cell therapy in preclinical models fail to translate to the clinical setting. This can be explained by crucial differences between the cellular types and pathophysiological mechanisms of the disease, as well as the differences between human patients and animal models. We discuss examples that demonstrate how the results from preclinical trials might have overestimated the efficacy of myocardial regeneration therapies. Future research should focus, not only on studying the best cell type to use but, very importantly, understanding the levels of safety and cellular interaction that can elicit efficient therapeutic effects in human tissue. Addressing the challenges associated with future research may ensure the success of stem cell therapy in improving preclinical models and the treatment of Chagas disease.

Interferon-γ and other inflammatory mediators in cardiomyocyte signaling during Chagas disease cardiomyopathy

Chagas disease cardiomyopathy(CCC), the main consequence of Trypanosoma cruzi(T.cruzi) infection, is an inflammatory cardiomyopathy that develops in up to 30% of infected individuals. The heart inflammation in CCC patients is characterized by a Th1 T cell-rich myocarditis with increased production of interferon(IFN)-γ, produced by the CCC myocardial infiltrate and detected at high levels in the periphery. IFN-γ has a central role in the cardiomyocyte signaling during both acute and chronic phases of T.cruzi infection. In this review, we have chosen to focus in its pleiotropic mode of action during CCC, which may ultimately be the strongest driver towards pathological remodeling and heart failure. We describe here the antiparasitic protective and pathogenic dual role of IFN-γ in Chagas disease.

Chagas heart disease:An overview of diagnosis,manifestations,treatment,and care

Chagas heart disease(CHD)affects approximately 30%of patients chronically infected with the protozoa Trypanosoma cruzi.CHD is classified into four stages of increasing severity according to electrocardiographic,echocardiographic,and clinical criteria.CHD presents with a myriad of clinical manifestations,but its main complications are sudden cardiac death,heart failure,and stroke.Importantly,CHD has a higher incidence of sudden cardiac death and stroke than most other cardiopathies,and patients with CHD complicated by heart failure have a higher mortality than patients with heart failure caused by other etiologies.Among patients with CHD,approximately 90%of deaths can be attributed to complications of Chagas disease.Sudden cardiac death is the most common cause of death(55%–60%),followed by heart failure(25%–30%)and stroke(10%–15%).The high morbimortality and the unique characteristics of CHD demand an individualized approach according to the stage of the disease and associated complications the patient presents with.Therefore,the management of CHD is challenging,and in this review,we present the most updated available data to help clinicians and cardiologists in the care of these patients.We describe the clinical manifestations,diagnosis and classification criteria,risk stratification,and approach to the different clinical aspects of CHD using diagnostic tools and pharmacological and non-pharmacological treatments.

Emerging and under-recognized Chagas cardiomyopathy in non-endemic countries

Due to recent population emigration movements,an epidemic of Chagas disease is currently menacing most developed countries.The authors report the case of a 53-year-old Brazilian woman living in Europe for the last 10 years who developed heart failure symptoms,having a previous symptomatic sinus node disease with a pacemaker implant at age of 40 years.The diagnosis was based on serology and myocardial biopsy and the patient was treated with nifurtimox.The authors emphasize the need of a high level of suspicion in patients with suggestive epidemiology and the needof populational screening of specific high risk groups.New treatment options are also discussed.

Birch Sap (<i>Betula alba</i>) and Chaga Mushroom (<i>Inonotus obliquus</i>) Extracts Show Anti-Oxidant, Anti-Inflammatory and DNA Protection/Repair Activity <i>In Vitro</i>

OBJECTIVE: The skin interacts strictly with the surrounding environment. Despite an efficient system of protection, its integrity is continuously assaulted by a massive group of external stresses. UV irradiations represent one of the most harmful factors for the cutaneous tissue. Both UV-A and UV-B can induce deep modifications of the different layers of the skin, including a weakening of its barrier function properties, DNA damages and degradation of the extracellular matrix. The aim of this project was to assess the UV protection activity of two natural compounds, the birch sap from Betula alba and organic extract from Inonotus obliquus (chaga mushroom) used separately or in a complex. METHODS: The anti-oxidant (ROS and MDA quantification, catalase and SOD activity measurement), anti-inflammatory (IL-1β, IL-6, IL-8, IL-10, TNF-α and INF-γ dosages) and the DNA protection/repair activities (DNA lesion site analysis) of birch sap and chaga mushroom extracts tested separately or in a complex containing organic birch sap 5% and Inonotus obliquus extracts 2% were evaluated in vitro after exposure of cultured keratinocytes and fibroblasts or reconstructed epidermis to UV-A/UV-B irradiations. RESULTS: We observed that birch sap from Betula alba and extracts from Inonotus obliquus prevent the formation of ROS and decrease the oxidative stress induced under UV irradiations, suggesting a strong anti-oxidant activity. In addition, the tested products showed an immunomodulatory effect by reducing the quantity of pro-inflammatory cytokines upon UV irradiations. UV-induced DNA damages of keratinocytes were also reduced by birch sap and chaga mushroom extracts. CONCLUSION: Here, for the first time, we have shown the photo-protection activity of extracts obtained from Betula alba and Inonotus obliquus mushroom on skin cells exposed to UV-A and UV-B irradiations. Due to their anti-oxidant, anti-inflammatory and DNA protection/repair activities, the tested products represent promising candidates in the development of cosmetic products with anti-photo-aging activity.

High resolution manometric findings in patients with Chagas' disease esophagopathy

Objective:To describe high resolution manometry features of a population of symptomatic- patients with Chagas’ disease esophagopathy(CDE).Methods:Sixteen symptomatic dysphagic patients with CDE[mean age(54.81±13.43) years,10 women]were included in this study.All patients underwent a high resolution manometry.Results:Mean lower esophageal sphincter(LES) extension was(3.02±1.17) cm with a mean basal pressure of(15.25±7.00) mmHg.Residual pressure was(14.31±9.19) mmHg.Aperistalsis was found in all 16 patients.Achalasia with minimal esophageal pressurization(type I) was present in 25%of patients and achalasia with esophageal compression(type 2) in 75%,according to the Chicago Classification.Upper esophageal sphincter(UES) mean basal pressure was(97.96±54.22) mmHg with a residual pressure of(12.95±6.42) mmHg.Conclusions:Our results show that LES was hypotensive or normotensive in the majority of the patients.Impaired relaxation was found in a minority of our patients.Aperistalsis was seen in 100%of patients.UES had impaired relaxation in a significant number of patients. Further clinical study is needed to investigate whether manometric features can predict outcomes following the studies of idiopathic achalasia..

The association of Triatoma maculata(Ericsson 1848) with the gecko Thecadactylus rapicauda(Houttuyn 1782)(Reptilia:Squamata:Gekkonidae):a strategy of domiciliation of the Chagas disease peridomestic vector in Venezuela?

Objective:To investigate the bioecological relationship between Chagas disease peridomestic vectors and reptiles as source of feeding.Methods:In a three-story building,triatomines were captured by direct search and electric vacuum cleaner search in and outside the building.Then,age structure of the captured Triatoma maculata(T.maculata) were identified and recorded.Reptiles living in sympatric with the triatomines were also searched.Results:T.maculata were found living sympatric with geckos(Thecadactylus rapicauda) and they bit residents of the apartment building in study.A total of 1 448 individuals of T.maculata were captured within three days,of which 74.2%(1 074 eggs) were eggs,21.5%were nymphs at different stages,and 4.3%were adults.Conclusions:The association of T.maculata and T.rapicauda is an effective strategy of colonizing dwellings located in the vicinity of the habitat where both species are present;and therefore,could have implications of high importance in the intradomiciliary transmission of Chagas disease.

Chagas Disease: Proposal of Health Education for Community Health Workers in the City of Petrolina, Pernambuco, Brazil

The Education for Health at PET Work Program (PET-Health) is focused on education as a pre-supposition. Actions are directed towards to the integration of service-learning and community. Interdisciplinary principle is directed from fusion of work of graduate students, academics and professionals of health services for the benefit of strengthening primary care and health surveillance. This work aimed to carry out educational activities with Community Health Agents (ACS) of the health facilities of PET-health, with the theme of Chagas disease. This descriptive cross-sectional study was carried out from January to May 2013, and the sample consisted of 25 active ACS in six Basic Health Units in the city of Petrolina, Brazil. In spite of actuation of ACS in primary care for over 10 years, a limited knowledge has been developed about this pathology. The health education workshops developed by the PET group clarified the ACS on Chagas disease allowing them to have an expansion of knowledge about the vector, habitat Barber, transmission, clinical manifestations… After the workshop, it was found that the ACS expanded their knowledge about the disease cycle, expanding the possibilities for action in the prevention of this pathology in their respective coverage areas. This work shows an important form of integration between education, service and community that can govern the new direction of health education.

A Decreased Expression and Functionality of Muscarinic Cholinergic Receptor in Acute Chagas Myocarditis

Background: Chagas disease is still a public health problem because of the remaining high prevalence, the expansion of the disease into developed countries and the re-emergences by oral transmission outbreaks. Chagas cardiomyopathy evolves as a consequence of an autonomic un-balance where the parasympathetic tone is undermined. Objective: To determine the functionality and expression of muscarinic cholinergic receptors in acute Chagas disease. Methodology: 62 male, 3-week-old Sprague Dawley rats were assayed;32 were infected with Trypanosoma cruzi trypo-mastigotes and 30 were healthy controls. Electrocardiographic studies were conducted in the absence or presence of direct muscarinic (oxotremorine and McN-A-343) or indirect agonists (phenylephrine) or antagonist (pirenzepine). Muscarinic M1 and M2 receptor expression was determined by radioligand [3H]-QNB binding assay and immunoblot. Results: Chagasic acute myocarditis was sustained by electrocardiographic signs and histopathological findings. Bradycardia induced by oxotremorine was significantly higher in healthy rats (HR) and the differences were enhanced by CsCl. In the absence of the agonist, CsCl induced a greater bradycardia in chagasic rats (ChR). In HR McN-A-343 induced tachycardia, however it induces bradycardia in the presence of a acetylcholinesterase inhibitor (neostigmine);no effects were observed in ChR. Pirenzepine induced a higher tachycardia in HR. Phenylephrine in the presence of pirenzepine induced a similar bradycardia in both groups, but recovery was faster in ChR. Muscarinic M1 and M2 receptor density was higher in HR. Conclusion: Muscarinic receptor expression and functionality are decreased in the acute Chagas disease that could impact the evolution and prognosis of the disease.

Surgical risk for patients with Chagasic achalasia and its correlation with the degree of esophageai dilation

AIM： To analyze the risk of cardiovascular complications in patients with indication for surgical treatment of Chagasic esophageal achalasia and to correlate the surgical risks with the degree of esophageal dilation, thereby proposing a risk scale index. METHODS： One hundred and twenty-four patients with Chagasic esophageal achalasia, who received surgical treatment at the Hospital das Clinicas of the Federal University of Goiás, were included in this study. The patients were mostly related to the postoperative complications due to the cardiovascular system. All the patients were submitted to： （1） clinical history to define the cardiac functional class （New York Heart Association）; （2） conventional 12-lead electrocardiogram at rest; and （3） contrast imaging of the esophagus to determine esophageal dilatation according to Rezende＇s classification of Chagasic megaesophagus. RESULTS： An assessment of the functional classification （FC） of heart failure during the preoperative period determined that 67 patients （54.03%） were assigned functional class Ⅰ （FC Ⅰ）, 46 patients （37.09%） were assigned functional class Ⅱ （FC Ⅱ）, and 11 patients （8.87%） were assigned functional class Ⅲ （FC Ⅲ）. None of the patients were assigned to functional class Ⅳ （FC Ⅳ）. There was a positive correlation between the functional class and the postoperative complications （FC Ⅰ×FC Ⅱ： P〈0.001; FC Ⅰ×FC Ⅲ： P〈0.001）. The ECG was normal in 44 patients （35.48%） and presented abnormalities in 80 patients （64.52%）. There was a significant statistical correlation between abnormal ECG （arrhythmias and primary change in ventricular repolarization） and postoperative complications （P〈0.001）. With regard to the classification of the Chagasic esophageal achalasia, the following distribution was observed： group Ⅱ, 53 patients （42.74%）; group Ⅲ, 37 patients （29.83%）; and group Ⅳ, 34 patients （27.41%）. There was a positive correlation between the degree of esophageal dilation and the increase in postoperative complications （grade Ⅱ×grade Ⅲ achalasia： P〈0.001; grade Ⅱ×grade Ⅳ achalasia： P〈0.001; and grade Ⅲ×grade Ⅳ achalasia： P = 0.017）. Analyzing these results and using a multivariate regression analysis associated with the probability decision analysis, a risk scale was proposed as follows： up to 21 points （mild risk）; from 22 to 34 points （moderate risk）; and more than 34 points （high risk）. The scale had 82.4% accuracy for mild risk patients and up to 94.6% for the high risk cases. CONCLUSION： The preoperative evaluation of the cardiovascular system, through a careful anamnesis, an ECG and contrast imaging of the esophagus, makes possible to estimate the surgical risks for Chagas＇ disease patients who have to undergo surgical treatment for esophageal achalasia.

Cardiomyopathy protection in Chagas Disease

There is some published evidence suggesting micro vascular endothelial dysfunction and dysautonomia involvement in Chagas disease in association with cardiomyocyte changes favoring disease progression. The combined treatment between angiotensin converting enzyme (ACE) inhibitor drugs;Simvastatin, muscarinic antibody immunoadsorbent together with fungicidal drugs would open therapeutic possibilities in this disease.

Chemical Control of Chagas Disease Vectors

This paper presents the reasons why countries to which Chagas disease is endemic should carry out the relevant research themselves. A local technical capability for a rational improvement in the chemical control of vectors is being developed. This research includes (1) the triatomicidal activity of chemical insecticides, (2) determination of the mechanisms of action of these chemicals, (3) search for new synergists of these insecticides, (4) development of fumigation canisters which may be more widely used, and (5) development of new chemicals with a greater potential for use as triatomicides. 1989 Academic Press, Inc.