Mitral valve prolapse and conduction disturbances: the forgotten association.

Various cardiac arrhythmias and conduction defects have been described in patients with mitral valve prolapse. We describe a case of a young woman affected by a mitral valve prolapse, involving the posterior mitral leaflet, with mild mitral regurgitation and an episode of syncope due to asystolia. It is hoped that this short communication will once again focus attention on the as yet unexplained association between mitral valve prolapse and various cardiac conduction disorders.

Role of host lysosomal associated membrane protein (LAMP) in Trypanosoma cruzi invasion and intracellular development.

Trypanosoma cruzi host cell entry depends on lysosomes for the formation of the parasitophorous vacuole. Lysosome internal surface is covered by two major proteins, highly sialilated, Lysosome Associated Membrane Proteins 1 and 2. T. cruzi, on the other hand, needs to acquire sialic acid from its host cell through the activity of trans-sialidase, an event that contributes to host cell invasion and later for parasite vacuole escape. Using LAMP1/2 knock out cells we were able to show that these two proteins are important for T. cruzi infection of host cells, both in entrance and intracellular development, conceivably by being the major source of sialic acid for T. cruzi.

Genetic analyses of Trypanosoma cruzi isolates from naturally infected triatomines and humans in northeastern Brazil.

Trypanosoma cruzi genetic diversity was investigated in 25 isolates (vectors and humans) from the semiarid zone of the State of Rio Grande do Norte, Brazil. Molecular markers (3' region of the 24Salpha rRNA; mitochondrial cytochrome oxidase subunit 2 (COII) gene; spliced leader intergenic region (SL-IR) gene; allelic size microsatellite polymorphism) identified 56% TcIII (100% Panstrongyluslutzi; 50% Triatomabrasiliensis); 40% TcII (91.7% humans; 50% T. brasiliensis) and 4% TcI (human). Microsatellite analysis revealed monoclonal and heterozygous patterns on one or more microsatellite loci in 64% of T. cruzi isolates (92.3% triatomines; 33.3% humans) and 36% putative polyclonal populations (66.7% humans; 7.7% triatomines) by loci SCLE10, SCLE11, TcTAT20, TcAAAT6, all belonging to TcII. Identical T. cruzi polyclonal profiles (88.9%) were detected, mostly from humans. The adaptative natural plasticity of TcII and TcIII and their potential for maintaining human infection in T. brasiliensis were confirmed. Intraspecific and phylogenetic T. cruzi diversity in the sylvatic and domestic transmission cycles in this specific region will provide exclusive control strategies.

Tako-tsubo-like left ventricular dysfunction: transient left ventricular apical ballooning syndrome.

AIMS/OBJECTIVES: This review examines the 'tako-tsubo-like' syndrome or transient left ventricular apical ballooning. The aim of this review is a complete evaluation of epidemiology, clinical and instrumental features, pathophysiological mechanisms, therapy and prognosis of this syndrome. METHODS: We have evaluated the data from literature for a comprehensive consideration of multiple aspects of this syndrome. RESULTS/FINDINGS: Transient left ventricular apical ballooning typically affects women, and the clinical presentation is comparable to acute coronary syndrome with chest pain or sudden dyspnoea, changes in ECG and elevated cardiac enzymes in the absence of significant coronary stenosis, with complete resolution of wall-motion abnormalities in a period of days or weeks. This syndrome is triggered by marked psychological or physiological stress. Several pathophysiological mechanisms have been proposed, such as cathecolamine-mediated cardiotoxicity, abnormalities in coronary microvascular function and multivessel coronary vasospasm. The highest incidence of transient left ventricular apical ballooning is in the Japanese population, but it has been recently identified also in the USA and Europe. Treatment is empirical and supportive. The prognosis is generally favourable, although some deaths have been reported, usually the result of irreversible cardiogenic shock, refractory ventricular arrhythmias, or other catastrophic cardiovascular event. CONCLUSIONS/INTERPRETATIONS: We conclude by emphasising the importance of a more deeper knowledge of this syndrome for general physicians and cardiologists and it should be often considered as a possible diagnosis occurring in emergency department and in patients admitted in the Chest Pain Units with a diagnosis of coronary acute syndrome.

A new consensus for Trypanosoma cruzi intraspecific nomenclature: second revision meeting recommends TcI to TcVI.

In an effort to unify the nomenclature of Trypanosoma cruzi, the causative agent of Chagas disease, an updated system was agreed upon at the Second Satellite Meeting. A consensus was reached that T. cruzi strains should be referred to by six discrete typing units (T. cruzi I-VI). The goal of a unified nomenclature is to improve communication within the scientific community involved in T. cruzi research. The justification and implications will be presented in a subsequent detailed report.

A quadricuspid aortic valve associated with severe aortic regurgitation and left ventricular systolic dysfunction.

We report a case of a quadricuspid aortic valve associated with severe aortic regurgitation and left ventricular systolic dysfunction.

Coronary artery fistula: diagnostic role of transthoracic and transesophageal echocardiography.

Congenital coronary artery fistulas (CAFs) are rare. Some patients develop symptoms of congestive heart failure secondary to a large left-to-right shunt or myocardial ischemia from coronary artery steal in the first few years after birth. After the second decade the frequency of symptoms and complications increase. We report a case of CAF originating from the circumflex artery and draining into the coronary sinus, associated with left main coronary aneurysm. Transtho-racic and transesophageal echocardiography approach showed the origin, course, and drainage site of the CAF. This case represents a typical sample of this rare anomaly and puts into evidence the essential role of echocardiography to define and complete the angiographic diagnosis.

Cell culture and animal infection with distinct Trypanosoma cruzi strains expressing red and green fluorescent proteins.

Different strains of Trypanosoma cruzi were transfected with an expression vector that allows the integration of green fluorescent protein (GFP) and red fluorescent protein (RFP) genes into the beta-tubulin locus by homologous recombination. The sites of integration of the GFP and RFP markers were determined by pulse-field gel electrophoresis and Southern blot analyses. Cloned cell lines selected from transfected epimastigote populations maintained high levels of fluorescent protein expression even after 6 months of in vitro culture of epimastigotes in the absence of drug selection. Fluorescent trypomastigotes and amastigotes were observed within Vero cells in culture as well as in hearts and diaphragms of infected mice. The infectivity of the GFP- and RFP-expressing parasites in tissue culture cells was comparable to wild type populations. Furthermore, GFP- and RFP-expressing parasites were able to produce similar levels of parasitemia in mice compared with wild type parasites. Cell cultures infected simultaneously with two cloned cell lines from the same parasite strain, each one expressing a distinct fluorescent marker, showed that at least two different parasites are able to infect the same cell. Double-infected cells were also detected when GFP- and RFP-expressing parasites were derived from strains belonging to two distinct T. cruzi lineages. These results show the usefulness of parasites expressing GFP and RFP for the study of various aspects of T. cruzi infection including the mechanisms of cell invasion, genetic exchange among parasites and the differential tissue distribution in animal models of Chagas disease.

Cardiac arrest in a patient with a mobile right atrial thrombus in transit and amyloidosis.

Primary amyloidosis is a rare disorder in which insoluble fibers are deposited in tissue and organs, impairing their function. Cardiac involvement occurs in up to 50% of patients with primary amyloidosis. We describe a case of a 75-year-old admitted to our department after he had a sudden cardiac arrest due to massive bilateral thrombotic occlusion of the pulmonary arteries. The echocardiogram revealed many atrial thrombi swirling inside the right atrium and protruding into the tricuspid valve partly occluding it. Severe concentric hypertrophy of the left ventricle was also present with a preserved ejection fraction. The right ventricle was dilated, hypertrophic and ipokinetic with a severe tricuspidal insufficiency that permitted estimation of a severe pulmonary hypertension. All these characteristics were highly suggestive for an infiltrative form of hypertrophic cardiomyopathy. The final diagnosis was amyloidosis.

Ubiquitylated Tax targets and binds the IKK signalosome at the centrosome.

Constitutive activation of the NF-kappaB pathway by the Tax oncoprotein plays a crucial role in the proliferation and transformation of HTLV-I infected T lymphocytes. We have previously shown that Tax ubiquitylation on C-terminal lysines is critical for binding of Tax to IkappaB kinase (IKK) and its subsequent activation. Here, we report that ubiquitylated Tax is not associated with active cytosolic IKK subunits, but binds endogenous IKK-alpha, -beta, -gamma, targeting them to the centrosome. K63-ubiquitylated Tax colocalizes at the centrosome with IKK-gamma, while K48-ubiquitylated Tax is stabilized upon proteasome inhibition. Altogether, these results support a model in which K63-ubiquitylated Tax activates IKK in a centrosome-associated signalosome, leading to the production of Tax-free active cytoplasmic IKK. These observations highlight an unsuspected link between Tax-induced IKK activation and the centrosome.

[Interactions between Tax of HTLV1 and cellular factors]. / L'oncoprotéine Tax du HTLV1 dans la cellule : des manipulations réciproques.

HTLV-1 is a human retrovirus responsible for adult T-cell leukemialymphoma, a monoclonal proliferation of CD4 + T lymphocytes. In addition to the genes encoding the structural proteins and enzymes, the HTLV-1 genome encodes non structural proteins that regulate viral expression as well as various cellular machineries.Among them, Tax has rapidly been identified as the protein responsible for HTLV-1 transforming properties. Tax promotes cell proliferation by activating or repressing cellular genes and by disturbing the mechanisms that control cell division, DNA integrity and apoptosis. These multiple functions rely on the ability of Tax to recruit cytoplasmic and nuclear proteins. The mechanisms involved in the targeting of Tax toward these subcellular sites are still incompletely understood. This review describes the recent data concerning the intracellular maturation of Tax and the control of its functions through posttranslational modifications.

Random amplified polymorphic DNA profiles of Trypanosoma cruzi isolates from chagasic patients with different clinical forms.

The genetic variability of 61 Trypanosoma cruzi isolates from 47 chronic chagasic patients of Minas Gerais state was analyzed by random amplified polymorphic DNA polymerase chain reaction (RAPD-PCR) using M13-40, lambdagt11-F, and L15996 primers. Cluster analysis by unweighted pair group method analysis was applied to RAPD profiles, and cluster analysis used to verify a possible correlation among different clinical forms of the disease from these patients. The T. cruzi isolates showed distinct grouping on tree topology, with the isolates not being possible to establish a correlation to the clinical forms of Chagas' disease. These data showed that the T. cruzi isolates from these patients would compose a group of populations well correlated genetically.

Further genetic characterization of the two Trypanosoma cruzi Berenice strains (Be-62 and Be-78) isolated from the first human case of Chagas disease (Chagas, 1909).

We describe here an extension of a previous genetic characterization of Trypanosoma cruzi strains (Be-62 and Be-78) isolated from the patient Berenice, the first human case of Chagas disease [Chagas, C., 1909. Nova Tripanomíase humana. Estudos sobre morfologia e o ciclo evolutivo do Schizotrypanum cruzi, n. gen., n. sp., agente etiolójico da nova entidade morbida do homem. Mem. Inst. Oswaldo Cruz 1, 159-218]. We wanted to verify the composition of T. cruzi populations originated from these two isolates. In the present work, 22 enzymatic loci (MLEE), nine RAPD primers and 7 microsatellite loci were analyzed. Clones from both strains were also characterized to verify whether these strains are mono or polyclonal. Be-62 and Be-78 strains were different in 3 out of 22 enzymatic systems, in 3 out of 9 RAPD primers tested and in all microsatellite loci investigated. However, our data suggests that both strains are phylogenetically closely related, belonging to genetic group 32 from Tibayrenc and Ayala [Tibayrenc, M., Ayala, F.J., 1988. Isoenzime variability in Trypanosoma cruzi, the agent of Chagas' disease: genetical, taxonomical, and epidemiological significance. Evolution 42, 277-292], equivalent to zymodeme 2 and T. cruzi II major lineage which, in Brazil, comprises parasites from the domestic cycle of the disease. Microsatellite analyses showed differences between the parental strains but suggested that both populations are monoclonal since each strain and their respective clones showed the same amplification products.

Biological activity of the aqueous extract of Lychnophora pinaster Mart.

Lyophilized aqueous extract (LAE) from Lychnophora pinaster Mart (Asteraceae) aerial parts was evaluated in the search of possible biological activities. LAE exhibited trypanocidal activity (113.62 mg/mL), but could not inhibit 5-lipoxygenase in vitro (17 percent of inhibition). LAE chemical characterization by HPLC with UV-Diode Array Detector showed the presence of caffeic acid, isochlorogenic acid, vitexin, isovitexin and quercetin, in comparison with authentic samples.

Influence of the long-term Trypanosoma cruzi infection in vertebrate host on the genetic and biological diversity of the parasite.

The influence of the long-term Trypanosoma cruzi infection in vertebrate host on the biological and genetic properties of the parasite was evaluated. Four T. cruzi isolates obtained from different chronic chagasic dogs infected with Berenice-78 T. cruzi strain during 2 and 7 years were comparatively analyzed. The long-term T. cruzi infection has led to alterations in parasitemia, virulence and pathogenicity of Be-78 strain for mice. These biological parameters varied from low to high in realation to the parental strain. Randomly amplified polymorphic DNA and isoenzyme profiles detected two distinct genetic groups of parasites. The first group included the parental strain and two T. cruzi isolates, and the second group the two other isolates. Interestingly, the isolates of the second group showed a reversibility of the genetic profile to the parental strain after 25 passages in mice. No correlation between the genetic groups and biological properties of the isolates was observed. Our findings confirmed the population heterogeneity of the Be-78 strain, and showed how differently it responds to the long-term infection in the same vertebrate hosts.

Skeletal muscle regeneration and Trypanosoma cruzi-induced myositis in rats.

Although Chagas' disease is known to provoke severe acute myositis, information on muscle regeneration is missing. The current paper shows that during T. cruzi infection in rats, skeletal muscle parasitism and the consequent inflammatory process are higher in muscle with a high proportion of type-I myofibres (soleus and diaphragm). Immunohistochemistry showed an acute inflammatory process characterized by ED1+ and ED2+ macrophages, CD8+ lymphocytes, and NK cells. Parasite-nest rupture provoked segmental degeneration of myofibres followed by regeneration. These phenomena were observed at both light and transmission electron microscopy levels. Myofibre regeneration involved activation of satellite cells assessed by the expression of MyoD, a muscle-specific transcription factor. Ultrastructural evidence of fusion of myoblast-like cells with the intact segment of degenerating fibres has been provided. At the chronic phase no signs of fibrosis were found, but sparse and small inflammatory foci were found. Our results argue against the relevant participation of autoimmunity phenomena in both acute and chronic phases and furnish a new view for explaining histopathological findings in human patient muscles.