In the late phase of Trypanosoma cruzi infection, parasite persistence and an exaggerated immune response accompanied by oxidative stress play a crucial role in the genesis of Chronic Chagasic ...Cardiomyopathy (CCC). Current treatments (Benznidazole (BNZ) and Nifurtimox) can effect only the elimination of the parasite, but are ineffective for late stage treatment and for preventing heart damage and disease progression. In vivo trypanocidal and cardioprotective activity has been reported for Lippia alba essential oils (EOs), ascribed to their two major terpenes, limonene and caryophyllene oxide. To investigate the role of antioxidant and immunomodulatory mechanisms behind these properties, chronic-T. cruzi-infected rats were treated with oral synergistic mixtures of the aforementioned EOs. For this purpose, the EOs were optimized through limonene-enrichment fractioning and by the addition of exogenous caryophyllene oxide (LIMOX) and used alone or in combined therapy with subtherapeutic doses of BNZ (LIMOXBNZ). Clinical, toxicity, inflammatory, oxidative, and parasitological (qPCR) parameters were assessed in cardiac tissue. These therapies demonstrated meaningful antioxidant and immunomodulatory activity on markers involved in CCC pathogenesis (IFN-γ, TNF-α, IL-4, IL-10, and iNOS), which could explain their significant trypanocidal properties and their noteworthy role in preventing, and even reversing, the progression of cardiac damage in chronic Chagas disease.
The present study aimed to characterize the histopathological findings and the phenotype of inflammatory cells in the myocardial tissue of patients with end-stage heart failure (ESHF) secondary to ...CCC in comparison with ESHF secondary to non-Chagas cardiomyopathies (NCC).
A total of 32 explanted hearts were collected from transplanted patients between 2014 and 2017. Of these, 21 were classified as CCC and 11 as other NCC. A macroscopic analysis followed by a microscopic analysis were performed. Finally, the phenotypes of the inflammatory infiltrates were characterized using flow cytometry.
Microscopic analysis revealed more extensive fibrotic involvement in patients with CCC, with more frequent foci of fibrosis, collagen deposits, and degeneration of myocardial fibers, in addition to identifying foci of inflammatory infiltrate of greater magnitude. Finally, cell phenotyping identified more memory T cells, mainly CD8+CD45RO+ T cells, and fewer transitioning T cells (CD45RA+/CD45RO+) in patients with CCC compared with the NCC group.
CCC represents a unique form of myocardial involvement characterized by abundant inflammatory infiltrates, severe interstitial fibrosis, extensive collagen deposits, and marked cardiomyocyte degeneration. The structural myocardial changes observed in late-stage Chagas cardiomyopathy appear to be closely related to the presence of cardiac fibrosis and the colocalization of collagen fibers and inflammatory cells, a finding that serves as a basis for the generation of new hypotheses aimed at better understanding the role of inflammation and fibrogenesis in the progression of CCC. Finally, the predominance of memory T cells in CCC compared with NCC hearts highlights the critical role of the parasite-specific lymphocytic response in the course of the infection.
Metodología: Los transferosomas fueron obtenidos mediante rehidratación de película lipídica. Ratas Wistar fueron tratadas tópica e intraperitonealmente con los transferosomas por 5 días. La ...penetración ex vivo fue determinada mediante el ensayo en celdas de Franz y la retención por el método de la cinta adhesiva. Cinco y treinta días postratamiento se obtuvo la piel y órganos para determinar la retención del compuesto y realizar estudios histopatológicos. La PcAlCl fue extraída con solventes y cuantificada por fluorometría. Los resultados se expresaron en nM PcAlCl/mg órgano. Conclusión: La PcAlCl contenida en transferosomas fue retenida principalmente en estrato córneo, mostrando bajas concentraciones en la dermis, sitio donde se aloja el parásito. Se sugiere modificar los componentes vesiculares del sistema para aumentar la permeación del compuesto.
•A successfully model of chronic Chagas disease was induced in rats.•An oral therapy was developed from fractions of Lippia alba essential oils.•Echocardiographycal and histopathological test ...confirmed a cardioprotective effect.•The therapy showed a trypanocidal action similar to Benznidazole by qPCR analysis.•The treatment scheme was apparently non-toxic by clinical and pathological test.
The present study reports the trypanocidal and cardioprotective properties of fractions derived from Lippia alba (Verbenaceae family) essential oils (EOs), in a murine model of chronic Chagas disease (ChD). This infection represents one of the most serious public health problems in Latin American countries, without an effective therapy for chronic infection and its eventual cardiac complications. In the model established herein, the therapeutic scheme which involved 30 oral and daily doses of OxiLim (a mix composed by fractions enriched in citral, caryophyllene oxide, and limonene) was not toxic and exhibited trypanocidal activity comparable to benznidazole (assessed by parasitic DNA quantification - qPCR); but with an additional protective effects against cardiomyopathy progression. This last finding was confirmed by both echocardiography (reduction in the maximum diameter of the cardiac silhouette), and heart histopathology (tissue recovery, abundant fibroblasts, and mild separation of cardiac fibers). Conversely, rats treated only with benznidazole showed a significant increase in cardiac diameter with severe fiber dilation, angiogenesis, and high diversity of immune infiltrate. This research reports a highly trypanocidal (similar to benznidazole) therapeutic scheme based on L. alba essential oil fractions (OxiLim), which also exhibits a positive cardioprotective effect in the course of chronic chagasic cardiomyopathy, in rats.
Benznidazole (BZL) and Nifurtimox (NFX) are the pharmacological treatment for acute phase Chagas Disease (CD); however, therapy resistance and residual mortality development remain important ...unresolved issues. Posaconazole (POS) has shown a trypanocidal effect in vivo and in vitro. Thus, this study aimed at comparing the T. Cruzi parasitic load-reducing effect of the combination of BZL+POS against that of monotherapy with either, during acute phase CD, in an experimental murine model.
Nineteen Wistar rats were randomly allocated to four groups and inoculated with the trypomastigotes of T. cruzi strain´s JChVcl1. The rats were administered anti-parasites from day 20-29 post-infection. The Pizzi and Brener method was used for parasitemia measurement. Longitudinal data analysis for the continuous outcome of repeated measures was performed using parasitemia as the outcome measured at days 20, 22, 24, 27, and 29 post-infection.
All four groups had similar parasitic loads (p=0.143) prior to therapy initiation. Among the three treatment groups, the BZL+POS (n=5) group showed the highest mean parasitic load reduction (p=0.000) compared with the control group. Likewise, the BZL+POS group rats showed an earlier therapeutic effect and were the only ones without parasites in their myocardial samples.
Treatment of acute phase CD with BZL+POS was more efficacious at parasitemia and myocardial injury reduction, compared with monotherapy with either.
Abstract
Background
HIV/AIDS-related infections are commonly presented in a disseminated form, compromising a high variety of organs and systems, mainly the Respiratory and Central Nervous System ...(CNS). In developing countries, the opportunistic agent spectrum varies from what is reported in the rest of the world, being the anatomical compromise also different from developed countries reports. In Colombia there has not been published any study that characterizes the anatomopathological findings of opportunistic infections in a sample of HIV/AIDS patients this size.
Methods
Descriptive retrospective study, adjusted to the current regulations on human research. A review of the autopsy protocols performed at the Department of Pathology of the Universidad Industrial de Santander (UIS) between 2004 and 2016 was executed, selecting those with HIV/AIDS and at least one opportunistic infection as the final diagnosis, of these there were evaluated the pathological findings and demographic variables.
Results
Among 3497 autopsy protocols reviewed, there were found 249 cases of HIV/AIDS associated to opportunistic infections, 183 men (73,5%) and 66 women (26,5%), with an average age of 37.94 ± 12.56 years. The main compromised systems were the Lower Respiratory Tract (LRT) with 184 cases (73,8%), mainly by M. tuberculosis (76 cases; 41,3%), followed by the Central Nervous System (CNS) with 95 cases (38,1%), mainly by Toxoplasma gondii (38 cases; 20,6%), and in third place the Lymphoreticular System (LRS) with 92 cases (50%), mainly by Histoplasma capsulatum (39 cases; 21,1%). Less prevalent agents like Trypanosoma cruzi were found compromising multiple systems, with 6 infecting the CNS and 7 causing Chagasic myocarditis.
Conclusion
Disseminated forms and simultaneous multiple agent compromise of one system are common features in HIV/AIDS patients, because of this the clinician must have a high level of suspicion for diagnosing coinfection when approaching a determinated organ or system compromised by an infectious agent.
Disclosures
All authors: No reported disclosures.
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