Mycobacterium bovis BCG as immunostimulating agent prevents the severe form of chronic experimental Chagas disease.

Introduction: There is currently no vaccine against Chagas disease (ChD), and the medications available confer multiple side effects. Mycobacterium bovis Bacillus Calmette-Guérin (BCG) produces balanced Th1, Th2, and Th17 modulatory immune responses and has improved efficacy in controlling chronic infections through nonspecific immunity. We aimed to improve the response to infection by inducing a stronger immune response and greater protection against the parasite by trained immunity. Methods: BALB/c mice were immunized with BCG subcutaneously, and 60 days later, they were infected with Trypanosoma cruzi intraperitoneally. An evaluation of the progression of the disease from the acute to the chronic stage, analyzing various aspects such as parasitemia, survival, clinical status, and humoral and cellular immune response, as well as the appearance of visceral megas and the histopathological description of target organs, was performed. Results: Vaccination reduced parasitemia by 70%, and 100% survival was achieved in the acute stage; although the presentation of clinical signs was reduced, there was no increase in the antibody titer or in the differential production of the isotypes. Conclusion: Serum cytokine production indicated a proinflammatory response in infected animals, while in those who received BCG, the response was balanced by inducing Th1/Th2-type cytokines, with a better prognosis of the disease in the chronic stage.

Early Estrogen Replacement Therapy Attenuates Cardiac Dysfunction Caused by Aging and Ovariectomy in Female Wistar Rats.

BACKGROUND: Cardiovascular diseases (CVDs) are the leading cause of women's mortality, linked to aging and reduced estrogen during menopause. Estrogen replacement therapy (ERT) is suggested for CVDs prevention. Yet, its timing initiation remains contentious. Thus, we aimed to evaluate the effect of early and late estrogen therapy on cardiac function and lipid metabolism in ovariectomized old female Wistar rats. METHODS: Fifty randomized female Wistar rats were included in 5 groups (n = 10, 18 months old): (1) Sham, (2) 10 weeks post ovariectomy (Ovx-10 w), (3) 10 weeks post Ovx + early estrogen replacement therapy (Ovx 10 w-early ERT), (4) 20 weeks post Ovx (Ovx-20 w) and (5) Ovx 20 w-late ERT. Three days (early ERT) or 10 weeks (late ERT) after surgery 17-ß estradiol was given (5 µg/kg/day), and 10 weeks after the start of ERT, we assessed cardiac function by echocardiography, electrocardiography, and cardiac catheterization. Estradiol, cholesterol, triglyceride (TG), high-density lipoprotein (HDL) and low-density lipoprotein (LDL) levels were determined. Cardiac histology was performed with Masson's staining. RESULTS: Ovariectomy (Ovx) increases left ventricle internal systolic diameter (0.4 vs 0.3 cm, *p = 0.020) and decreases shortening fraction (40 vs 54 %, *p = 0.030) regardless of therapy. ERT prevents the increase in left ventricle mass after 10 weeks post-Ovx and the ejection fractionreduction after 20 weeks. Lower P wave amplitudes (18.8 vs 24.2 ms, *p = 0.013) were found in the Ovx-20 w group. A longer duration of the QRS complex after 20 weeks post-Ovx with and without ERT was found (32.5 and 32.1 vs 28.3 ms, *p = 0.003; *p = 0.007). Diastolic blood pressure was higher 20 weeks post-Ovx (86 vs 76 mmHg, *p = 0.047), regardless of ERT. The left ventricle (LV) -dP/dt was decreased in Ovx groups without ERT (-750 vs -1320 mmHg, *p = 0.034). An increase in LV collagen deposition was found in the Ovx 10 w group vs Sham (9.58 vs 4.54 %, *p = 0.028). Early ERT avoids the increase in body weight, cholesterol and LDL caused by Ovx. CONCLUSIONS: Ovariectomy causes time-dependent alterations in lipid metabolism, morphology, electrical activity, and heart contractile function. Early but not late ERT prevents some of these effects.

"Bronchogenic cyst impersonating a pericardial lesion": A case report.

A 32-year-old female presented with palpitations and chest discomfort. The patient had a history of pericardiotomy due to pericardial effusion. Multimodal imaging, including echocardiography, cardiac magnetic resonance (CMR), and coronary computed tomography angiography (CCTA) showed a single mass in the pericardium as the cause of the symptoms. Furthermore, its location and potential complications were accurately defined. The patient underwent a successful surgical resection of the pericardial cyst, microscopic histopathological examination was compatible with a bronchogenic cyst, a very rare congenital malformation. The article discusses the rarity of bronchogenic cysts in the pericardium and the importance of accurate diagnosis and appropriate treatment.

Hypertrophic cardiomyopathy in the systemic right ventricle in a patient with congenitally corrected transposition of the great arteries: A case report.

Congenitally corrected transposition of the great arteries is a rare clinical entity, which usually presents during adulthood with associated defects; atrioventricular block, heart failure, systemic valve failure, and arrhythmias usually complicate the clinical course. Even rarer is associated hypertrophic cardiomyopathy, which complicates the disease course and clinical decision-making. Herein, we present a patient with this condition who underwent heart transplantation, with adequate clinical resolution.

Nitazoxanide: A Drug Repositioning Compound with Potential Use in Chagas Disease in a Murine Model.

Chagas disease (ChD), caused by Trypanosoma cruzi, is the most serious parasitosis in the western hemisphere. Benznidazole and nifurtimox, the only two trypanocidal drugs, are expensive, difficult to obtain, and have severe side effects. Nitazoxanide has shown to be effective against protozoa, bacteria, and viruses. This study aimed to evaluate the nitazoxanide efficacy against the Mexican T. cruzi Ninoa strain in mice. Infected animals were orally treated for 30 days with nitazoxanide (100 mg/kg) or benznidazole (10 mg/kg). The clinical, immunological, and histopathological conditions of the mice were evaluated. Nitazoxanide- or benznidazole-treated mice had longer survival and less parasitemia than those without treatment. Antibody production in the nitazoxanide-treated mice was of the IgG1-type and not of the IgG2-type as in the benznidazole-treated mice. Nitazoxanide-treated mice had significantly high IFN-γ levels compared to the other infected groups. Serious histological damage could be prevented with nitazoxanide treatment compared to without treatment. In conclusion, nitazoxanide decreased parasitemia levels, indirectly induced the production of IgG antibodies, and partially prevented histopathological damage; however, it did not show therapeutic superiority compared to benznidazole in any of the evaluated aspects. Therefore, the repositioning of nitazoxanide as an alternative treatment against ChD could be considered, since it did not trigger adverse effects that worsened the pathological condition of the infected mice.

Assessment of Left Ventricular Myocardial Fibrosis in Adult Patients With Ebstein Anomaly: A Retrospective Cohort Study Based on Cardiac Magnetic Resonance and Histopathological Samples.

BACKGROUND: The association between Ebstein anomaly and myocardial fibrosis, particularly in the left ventricle, has been controversial. We aimed to assess the prevalence of replacement fibrosis with a focus on the left ventricle (LV) using cardiac magnetic resonance (CMR), make a histopathological association between LV fibrosis and CMR findings, and explore whether LV fibrosis is an independent risk factor for cardiovascular disease mortality using a derived risk score. METHODS: We performed a 12-year (2009-2021) retrospective cohort of adult patients with Ebstein anomaly who underwent CMR. The CMR evaluation included a comprehensive assessment of myocardial fibrosis by late gadolinium enhancement (LGE). Four postmortem samples were obtained from our cohort and stained using Masson trichrome to characterize LV fibrosis. We used Cox-regression analysis to identify and derive a prediction score that associated LV fibrosis with cardiovascular disease mortality. RESULTS: We included 57 adults with Ebstein anomaly (52% men; median age, 29.52 [interquartile range, 21.24-39.17] years), of whom 12 died during follow-up. LGE prevalence by CMR was observed in 52.6% in any chamber; LV-LGE in 29.8%. Histopathological findings revealed a mid-wall pattern with predominantly interstitial fibrosis and minimal replacement fibrosis. LV-LGE was associated with increased risk of cardiovascular disease mortality (hazard ratio, 6.02 [95% CI, 1.22-19.91]) attributable to lateral and mid-wall LV segment involvement. Our mortality score achieved an overall good prediction capacity (R2, 0.435; C statistic, 0.93; Dxy, 0.86). CONCLUSIONS: There is a high prevalence of LV fibrosis replacement in adults with Ebstein anomaly, characterized by specific CMR and histological patterns. Furthermore, LV-LGE fibrosis is an independent predictor of cardiovascular disease mortality, which could be integrated into risk assessment in clinical management.

Histopathological maladaptive changes in the explanted human mitral leaflets correlate with changes in echocardiographic leaflet morphology and the severity of ischaemic mitral regurgitation.

AIMS: Several changes of the mitral valve (MV) morphology have been previously documented in ischaemic mitral regurgitation (IMR) upon macro and microscopic examination. This study aimed to correlate echocardiographic MV thickening with IMR severity and to delineate the histopathological basis of valve thickening from the explanted leaflets. METHODS AND RESULTS: Two hundred and fifty patients were included in the echo-group; of these, 48 patients (19.2%) underwent surgical mitral valve replacement (MVR), including them in the histology-group. By echocardiography, the thickness of the anterior and posterior leaflet was more extensive in moderate to severe IMR, P < 0.001. Histology-group: patients were divided into two groups based on the median thickness: those with cusp thickness <0.42 cm in Group 1, and ≥0.42 cm in Group 2. The thickness of the base and cusp was more significant in Group 2, P < 0.05 in both. Group 2 biopsies were characterized by involvement of the three leaflet segments, myxoid tissue, and fibrosis deposition. Thicker leaflets were associated with a greater degree of mitral regurgitation (MR), P < 0.0001. In the echo-group, a median leaflet thickness of 3.5 mm of the anterior and posterior MV was independently associated with moderate to severe ischaemic MR [odds ratio (OR) 2.88, P < 0.01] and (OR 10.8, P < 0.001), respectively. CONCLUSION: In ischaemic MR, the thicker the cusps, the worse the MR. Leaflet thickening was due to the myxoid and fibrosis deposition and was detected by echocardiography. Therefore, this method can be helpful in the evaluation of valve remodelling.

Prenatal Diagnosis and Outcome of Intrapericardial Teratoma: Report of Two Clinical Scenarios.

Intrapericardial teratoma is a rare tumor composed of tissue from the three germ cell layers with a rapid growth that may cause severe hemodynamic complications due to compressive effects. We present two clinical cases: the first case had severe fetal heart failure with fatal outcome, and the second underwent surgical treatment during the immediate postnatal period with a favorable evolution. Although teratomas are histologically benign tumors, rapid growth can cause serious hemodynamic complications. The importance of prenatal diagnosis is to allow appropriate monitoring of tumor growth and establish a prompt therapeutic plan. Opportune surgical treatment can prevent death and improve the prognosis of these patients.

Acute Mitral Regurgitation Due to Chordae Tendineae Rupture: A Rare Presentation of Cardiac Amyloidosis.

BACKGROUND In cardiac amyloidosis (CA), misfolded proteins deposit in the extracellular space of cardiac tissue. These deposits classically cause restrictive cardiomyopathy with diastolic dysfunction. Although there are at least 30 proteins known to cause amyloid aggregates, 2 main types make up most diagnosed cases: light chain amyloidosis (AL) and transthyretin amyloidosis (ATTR). Since CA is considered a rare condition, it is often underdiagnosed or recognized in the advanced stages. Once amyloid deposits involve the heart tissue, they are associated with a worse outcome and higher mortality rates, especially in patients presenting symptoms of heart failure. CASE REPORT We report a case of a 22-year-old man presenting with acute severe mitral regurgitation, secondary to posterior mitral leaflet chordae tendineae rupture (CTR). Surgical mitral valve replacement with a mechanical prosthesis was performed, and cardiac tissue biopsy samples were obtained. After surgery, the patient improved significantly but suddenly presented with hemodynamic deterioration, until he died due to severe hemodynamic compromise and multiorgan failure. Although the etiology of the CTR was not established before surgical intervention, the histopathological analysis suggested CA. CONCLUSIONS CA diagnosis can be complex, especially in a 22-year-old-man with atypical clinical and imaging manifestations. In this patient, other differential diagnoses were considered, since CA presenting in a young patient is a rare phenomenon and acute mitral regurgitation secondary to CTR presents more frequently in other heart conditions. Furthermore, rapid postoperative deterioration resulted in the patient's death before biopsy samples were available because suspicion of amyloidosis had not been raised until that point.

Case Report: Unusual Cause of Chest Pain: A Multi-Image Assessment of a Cardiac Mass.

Myxomas represent the most common benign primary cardiac tumor, they usually grow out of the interatrial septum into the left atrium with a pedunculated base. Intracardiac masses can be found incidentally on imaging studies, but symptomatology may arise secondary to the mass effect, embolization, and valvular function impairment. We present the case of a 75-year-old woman who arrived at the emergency department with atrial fibrillation and NSTEMI segment elevation myocardial infarction (NSTEMI) secondary to a highly vascularized neoplasm visible by coronary angiography and angiotomography. Scarce reports show high quality multi-imaging assessment of significantly vascularized myxomas with such atypical presentation. High-definition imaging studies played a fundamental role in the surgeon's management of a mass with a complex neovascularization.

Right Heart Chambers Longitudinal Strain Provides Enhanced Diagnosis and Categorization in Patients With Pulmonary Hypertension.

Background: Increased systolic pulmonary arterial pressure (sPAP) could lead to the mechanical dysfunction and myocardial fibrosis of the right heart chambers. Echocardiographic strain analysis has not been adequately studied in patients with pulmonary hypertension (PH). Study design and methods: A cross-sectional cohort of patients with suspected PH and echocardiographic strain evaluation was recruited. The cut-off values of peak tricuspid regurgitation velocity (TRV) with the low probability of PH (≤2.8 m/s), intermediate probability (2.9-3.4 m/s, without other echo PH signs), and high probability of PH (2.9-3.4 m/s with other echo PH signs and >3.4 m/s) categories were studied by right ventricular and right atrial (RA) strain analysis in a sample of 236 patients. Results: The results showed that 58 (56.9%) patients had low, 15 (14.7%) had intermediate, and 29 (28.4%) had a high probability of PH. We observed a negative association between right ventricular free wall strain (RV-FWS) and atrial global strain with sPAP. With the increase in PH severity, RA reservoir, conduit, and contraction (booster) strain values decreased. The identified cut-off values of strain parameters had an adequate ability to detect PH severity categories. In addition, the post-mortem biopsies of right heart chambers from subjects with known severe PH were analyzed to quantify myocardial fibrosis. Our sample of right heart biopsies (n = 12) demonstrated an association between increased sPAP before death and right ventricular and RA fibrosis. Conclusion: Mechanical dysfunction and fibrosis in the right chambers are associated with increased sPAP. Right ventricular and atrial strain could provide enhancement in the diagnosis and categorization of subjects with suspected PH.

Histopatología y Strain auricular en pericarditis constrictiva y miocardiopatía restrictiva / Histopathology and Atrial Strain in Constrictive Pericarditis and restrictive cardiomyopathy

Resumen La pericarditis constrictiva y la miocardiopatía restrictiva son enfermedades raras caracterizadas por síntomas de insuficiencia cardíaca congestiva. El objetivo de este estudio es mostrar el diagnóstico diferencial de estas dos patologías, mediante strain auricular y establecer su correlación con la histopatología de corazones correspondientes. Se analizan 2 casos clínicos representativos de cada una de estas patologías. Se analizan sus presentaciones clínicas, los datos ecocardiograficos y en ambos casos se realizaron biopsias endomiocardicas con lo cual se presenta la correlación histológica. El strain auricular permitió evaluar la afección de las aurículas, consideramos que el strain auricular disminuido podría estar relacionado con la presencia de fibrosis.

Abstract Histopathology and Atrial Strain in Constrictive Pericarditis and restrictive cardiomyopathy Constrictive pericarditis and restrictive cardiomyopathy are rare diseases characterized by congestive heart failure symptoms. The aim of this study is to show the differential diagnosis of these two pathologies using strain and to establish their correlation with histopathology of the corresponding hearts. Two representative clinical cases of each of these pathologies are analyzed. Their clinical presentations, echocardiographic data, and endomyocardial biopsies were performed in both cases, thus presenting the histological correlation. Atrial strain allowed us to evaluate the affection of the atria, we consider that decreased atrial strain could be related to the presence of fibrosis.

Electrolyzed Oxidizing Water Modulates the Immune Response in BALB/c Mice Experimentally Infected with Trypanosoma cruzi.

Chagas disease is a major public health problem in Latin America. The mixed Th1/Th2 immune response is required against Trypanosoma cruzi. Electrolyzed oxidizing water (EOW) has been shown to have germicidal efficacy. The objective of this study was to evaluate the EOW effectiveness in T. cruzi-infected BALB/c mice clinically, immunologically, and histologically. The severity of the infection was assessed by parasitaemia, general health condition, mortality, mega syndromes, and histological lesions. IgG, TNF-alpha, IFN-gamma, and IL-1 beta levels were quantified. The EOW administration showed a beneficial effect on parasitaemia, general physical condition, and mortality. High levels of IgG1 at 50 days postinfection were observed. Prophylactic EOW treatment was able to induce a predominantly TH1 immune response based on an IgG2a levels increase at the late acute phase, and a 10-fold increase of INF-gamma in whole acute phase. EOW was able to control the acute phase infection as effectively as benznidazole. Splenomegaly was caused by EOW treatment and lymphadenopathy was stimulated by T. cruzi infection in all groups. Severe tissue damage was not prevented by EOW treatments. Moderate efficacy may be due to immunomodulatory properties and not to a direct toxic effect on the parasite.

Design, manufacture and initial tests of a drug-eluting coronary stent.

INTRODUCTION: A drug-eluting coronary stent is being developed at the National Institute of Cardiology of Mexico for the treatment of ischemic heart disease. OBJECTIVE: To establish the best animal model for the tests, to show the advances in the drug-eluting stent prototype, to assess two drugs' antiproliferative activity and histological results. METHOD: Smooth muscle cell culture tests were performed in order to assess sirolimus and paclitaxel antiproliferative properties. The drugs were encapsulated inside the polymeric matrix of the stents. Rabbits and pigs were used as animal models. RESULTS: Sirolimus and paclitaxel showed an inhibitory effect, which was higher for the latter. Infrared spectroscopy and light and optical microscopy showed that the drug/polymer layer properly adhered to the stent. At a four-week follow-up, both animal models showed satisfactory clinical evolution and adequate histological response, although the porcine model was shown to be more suitable for future protocols. CONCLUSIONS: Preliminary tests of the drug-eluting stent provided bases for the development of a study protocol with an adequate number of pigs and with clinical angiographic and histopathological three-month follow-up.

INTRODUCCIÓN: En el Instituto Nacional de Cardiología de México se desarrolla una endoprótesis (stent) coronaria liberadora de fármacos para el tratamiento de la cardiopatía isquémica. OBJETIVO: Establecer el mejor modelo animal para las pruebas, mostrar los avances en el prototipo del stent liberador de fármacos, evaluar la actividad antiproliferativa de dos fármacos y los resultados histológicos. MÉTODO: Se realizaron cultivos de células de músculo liso para evaluar las propiedades antiproliferativas de sirolimus y paclitaxel. Los fármacos fueron encapsulados en el interior de la matriz polimérica de los stents. Se emplearon conejos y cerdos como modelos animales. RESULTADOS: Sirolimus y paclitaxel mostraron efecto inhibitorio, mayor en el segundo. La espectroscopia infrarroja y la microscopia óptica y electrónica mostraron que la capa del polímero con el fármaco se adhería adecuadamente al stent. A las cuatro semanas de seguimiento, ambos modelos animales mostraron evolución clínica satisfactoria y adecuada respuesta histológica, si bien el modelo porcino resultó más conveniente para protocolos futuros. CONCLUSIONES: Las pruebas preliminares del stent liberador de fármaco brindó bases para desarrollar el protocolo con un número adecuado en cerdos y con seguimiento clínico angiográfico e histopatológico a tres meses.

Design, manufacture and initial tests of a drug-eluting coronary stent / Diseño, fabricación y pruebas iniciales de una endoprótesis coronaria liberadora de fármaco

Abstract Introduction: A drug-eluting coronary stent is being developed at the National Institute of Cardiology of Mexico for the treatment of ischemic heart disease. Objective: To establish the best animal model for the tests, to show the advances in the drug-eluting stent prototype, to assess two drugs’ antiproliferative activity and histological results. Method: Smooth muscle cell culture tests were performed in order to assess sirolimus and paclitaxel antiproliferative properties. The drugs were encapsulated inside the polymeric matrix of the stents. Rabbits and pigs were used as animal models. Results: Sirolimus and paclitaxel showed an inhibitory effect, which was higher for the latter. Infrared spectroscopy and light and optical microscopy showed that the drug/polymer layer properly adhered to the stent. At a four-week follow-up, both animal models showed satisfactory clinical evolution and adequate histological response, although the porcine model was shown to be more suitable for future protocols. Conclusions: Preliminary tests of the drug-eluting stent provided bases for the development of a study protocol with an adequate number of pigs and with clinical angiographic and histopathological three-month follow-up.

Resumen Introducción: En el Instituto Nacional de Cardiología de México se desarrolla una endoprótesis (stent) coronaria liberadora de fármacos para el tratamiento de la cardiopatía isquémica. Objetivo: Establecer el mejor modelo animal para las pruebas, mostrar los avances en el prototipo del stent liberador de fármacos, evaluar la actividad antiproliferativa de dos fármacos y los resultados histológicos. Método: Se realizaron cultivos de células de músculo liso para evaluar las propiedades antiproliferativas de sirolimus y paclitaxel. Los fármacos fueron encapsulados en el interior de la matriz polimérica de los stents. Se emplearon conejos y cerdos como modelos animales. Resultados: Sirolimus y paclitaxel mostraron efecto inhibitorio, mayor en el segundo. La espectroscopia infrarroja y la microscopia óptica y electrónica mostraron que la capa del polímero con el fármaco se adhería adecuadamente al stent. A las cuatro semanas de seguimiento, ambos modelos animales mostraron evolución clínica satisfactoria y adecuada respuesta histológica, si bien el modelo porcino resultó más conveniente para protocolos futuros. Conclusiones: Las pruebas preliminares del stent liberador de fármaco brindó bases para desarrollar el protocolo con un número adecuado en cerdos y con seguimiento clínico angiográfico e histopatológico a tres meses.

DNA Vaccine Treatment in Dogs Experimentally Infected with Trypanosoma cruzi.

Chagas disease is a chronic and potentially lethal disorder caused by the parasite Trypanosoma cruzi, and an effective treatment has not been developed for chronic Chagas disease. The objective of this study was to determine the effectiveness of a therapeutic DNA vaccine containing T. cruzi genes in dogs with experimentally induced Chagas disease through clinical, pathological, and immunological analyses. Infection of Beagle dogs with the H8 T. cruzi strain was performed intraperitoneally with 3500 metacyclic trypomastigotes/kg body weight. Two weeks after infection, plasmid DNA immunotherapy was administered thrice at 15-day intervals. The clinical (physical and cabinet studies), immunological (antibody and cytokine profiles and lymphoproliferation), and macro- and microscopic pathological findings were described. A significant increase in IgG and cell proliferation was recorded after immunotherapy, and the highest stimulation index (3.02) was observed in dogs treated with the pBCSSP4 plasmid. The second treatment with both plasmids induced an increase in IL-1, and the third treatment with the pBCSSP4 plasmid induced an increase in IL-6. The pBCSP plasmid had a good Th1 response regulated by high levels of IFN-gamma and TNF-alpha, whereas the combination of the two plasmids did not have a synergistic effect. Electrocardiographic studies registered lower abnormalities and the lowest number of individuals with abnormalities in each group treated with the therapeutic vaccine. Echocardiograms showed that the pBCSSP4 plasmid immunotherapy preserved cardiac structure and function to a greater extent and prevented cardiomegaly. The two plasmids alone controlled the infection moderately by a reduction in the inflammatory infiltrates in heart tissue. The immunotherapy was able to reduce the magnitude of cardiac lesions and modulate the cellular immune response; the pBCSP treatment showed a clear Th1 response; and pBCSSP4 induced a balanced Th1/Th2 immune response that prevented severe cardiac involvement. The pBCSSP4 plasmid had a better effect on most of the parameters evaluated in this study; therefore, this plasmid can be considered an optional treatment against Chagas disease in naturally infected dogs.

Histological and Mechanical Behavior of INC 01 and 02 Bare Metal Stents Against a Commercial Stent: A Preclinical Study in a Porcine Model.

BACKGROUND: PCI is an expensive procedure in our population and it implies a huge cost for the institutions and National Health Service. AIM OF THE STUDY: The main objective was to evaluate the technical and biological success of two stents designed in Mexico. METHODS: Ten York pigs, 4-6 months of age, underwent implantation of the bare metal INC-01 (10 stents) and INC-02 (6 stents) coronary stent in addition to a conventional commercial stent (10 stents). Technical success was evaluated immediately with angiography and Intravascular Ultrasound IVUS, continued by a mean follow-up of 4 month and a final angiographic, IVUS and histological evaluation. RESULTS: Initial technical success, angiography and IVUS between the three stents were not significant. One stent presented restenosis in follow-up (commercial stent), but all other stents presented excellent clinical outcome, satisfactory angiographic and IVUS results. Inflammation, proliferation and endothelialization between the stents had no major differences in histological analysis in a mean of 4 months follow-up. CONCLUSIONS: In this pig model, the INC 01 and INC 02 stents showed the same delivering technical success, angiographic and IVUS features, biological and histological response compared to commercial last generation stents.

Atorvastatin and Fenofibrate Exert Opposite Effects on the Vascularization and Characteristics of Visceral Adipose Tissue in New Zealand White Rabbits.

Statins may precipitate the onset of type 2 diabetes (T2D) in high-risk patients. In contrast, only the subset of individuals with insulin resistance and/or diabetes receives cardiovascular benefits with fibrates. In this context, previous observations from our laboratory suggested that atorvastatin induced an increase in visceral adipose tissue (VAT), whereas fenofibrate had the opposite effects in rabbits. Therefore, we determined the mass, morphology, and vascularization of VAT in New Zealand white rabbits (n = 6/group) that received 0.33 or 2.6 mg/kg/d of atorvastatin or fenofibrate, respectively, during 2 months. As expected, the cholesterol from the atorvastatin group was lower after treatment, while triglycerides decreased in the fenofibrate group. The mass of VAT from the fenofibrate group was 46% lower compared to the controls, meanwhile atorvastatin was associated with a larger diameter of adipocytes (+65%) than that of the control and fenofibrate groups. Fibroblast growth factor 2 (FGF2) gene expression was lower in the fenofibrate group than in the control group (-54%). By contrast, vascular endothelial growth factor A (VEGF-A) gene expression in fenofibrate-treated rabbits was 110% higher than in the control group. In agreement with the gene expression, the marker of angiogenesis platelet endothelial cell adhesion molecule 1 was slightly but significantly higher (+10%) in rabbits treated with fenofibrate than in controls, as determined by immunohistochemistry. These results suggest that fenofibrate is associated with a favorable remodeling of VAT, that is, reduced mass and increased vascularization in normolipemic rabbits; in contrast, atorvastatin induced a nonfavorable remodeling of VAT. These results may be related to the cardiovascular benefits of fenofibrate and the increased risk of T2D in high-risk patients induced by atorvastatin.

Recombinant Enolase of Trypanosoma cruzi as a Novel Vaccine Candidate against Chagas Disease in a Mouse Model of Acute Infection.

Trypanosoma cruzi is the protozoan parasite that causes Chagas disease, which is considered by the World Health Organization to be a neglected tropical disease. Two drugs exist for the treatment of Chagas disease, nifurtimox and benznidazole; they are only effective in the acute phase, and a vaccine is currently not available. In this study, we used the recombinant enolase from T. cruzi H8 strain (MHOM/MX/1992/H8 Yucatán) (rTcENO) and its encoding DNA (pBKTcENO) to immunize mice and evaluate their protective effects in an experimental murine model of acute phase infection. Our results showed that mice vaccinated with rTcENO or its encoding DNA were able to generate typical specific antibodies (IgG1, IgG2a, and IgG2b), suggesting that a mixed Th1/Th2 immune response was induced. The parasite burden in the blood was reduced to 69.8% and 71% in mice vaccinated with rTcENO and pBKTcENO, respectively. The group vaccinated with rTcENO achieved 75% survival, in contrast to the group vaccinated with pBKTcENO that showed no survival in comparison to the control groups. Moreover, rTcENO immunization elevated the production of IFN-γ and IL-2 after the parasite challenge, suggesting that the Th1-type immune response was polarized. These results indicated that rTcENO could be used as a vaccine against Chagas disease.