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

peer reviewedAIMS: 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

Orígenes del conocimiento de la estructura y función del sistema cardiovascular

El léxico anatómico más antiguo se estableció por los sacerdotes egipcios, quienes ofrecían de forma ritual a los dioses todas las partes del cuerpo del difunto. Hacia el año 500 a. c. se iniciaron estudios de anatomía comparada por el médico Alcmeón de Crotona, autor del texto que, según Laín Entralgo, inicia formalmente la historia universal de la patología científica. Solamente en el siglo III a. C. en el Egipto tolemaico comenzaron a efectuarse disecciones en cadáveres humanos. En la época romana y en la Alta Edad Media, los médicos realizaban estudios anatómicos en humanos para descartar o confirmar sospechas de envenenamiento y en animales (monos, cerdos, etcétera) para extrapolar sus hallazgos al hombre. Pero en la Baja Edad Media (siglo XIV), se volvió al estudio directo del cuerpo humano. Dicho estudio alcanzó un gran auge en el siglo XVI, lo que llevó al descubrimiento de la circulación menor y, más tarde, de la circulación mayor de la sangre. En el siglo XVII llegó el estudio de la anatomía microscópica y, en el siglo XVIII, la sistematización de la anatomía patológica. En el siglo siguiente se impuso el cotejo anatomoclínico y, actualmente, se impone el auxilio de procedimientos tecnológicos de gabinete

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

Cotejo electro-histológico en un caso de miocardiopatía chagásica crónica

Se presenta el caso de un hombre de 50 años, campesino proveniente de una zona endémica de enfermedad chagásica, que padecía de miocardiopatía dilatada, verosímilmente chagásica. Este enfermo llegó en insuficiencia cardíaca y falleció a los pocos días. En el mismo día de su defunción, pudo registrarse un ECG y efectuar la necropsia. El ECG proporcionó signos de dilatación de las cámaras cardíacas, de miocardio inactivable con localización subendocárdica, en regiones anterolaterales del ventrículo izquierdo, y de lesión subepicárdica extensa. El examen anatómico demostró la dilatación de las cuatro cavidades cardíacas y la existencia de fibrosis subendocárdica localizada esencialmente en porciones anterolaterales del ventrículo izquierdo. El estudio histológico reveló la correspondencia de la distribución de los focos inflamatorios con la de la lesión mencionada: regiones epicárdicas y subepicárdicas del ventrículo izquierdo. A su vez la inoculación de Trypanosoma cruzien ratones provocó la formación de focos de inflamación linfocitaria netamente predominantes en regiones epicárdicas y subepicárdicas de los ventrículos

A Single Zidovudine (AZT) Administration Delays Hepatic Cell Proliferation by Altering Oxidative State in the Regenerating Rat Liver

The 3′-azido-3′-deoxythymidine or Zidovudine (AZT) was the first antiretroviral drug used in the treatment of HIV patients, which has good effectiveness but also hepatotoxic side effects that include cell cycle arrest and oxidative/nitrative mitochondrial damage. Whether such an oxidative damage may affect the proliferative-regenerative capacity of liver remains to be clearly specified at doses commonly used in the clinical practice. In this study, we described the oxidative-proliferative effect of AZT administered at a common clinical dose in rat liver submitted to 70% partial hepatectomy (PH). The results indicate that AZT significantly decreased DNA synthesis and the number of mitosis in liver subjected to PH in a synchronized way with the promotion of organelle-selective lipid peroxidation events (especially those observed in plasma membrane and cytosolic fractions) and with liver enzyme release to the bloodstream. Then at the dose used in clinical practice AZT decreased liver regeneration but stimulates oxidative events involved during the proliferation process in a way that each membrane system inside the cell preserves its integrity in order to maintain the cell proliferative process. Here, the induction of large amounts of free ammonia in the systemic circulation could become a factor capable of mediating the deleterious effects of AZT on PH-induced rat liver regeneration

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

Immunohistochemical diagnosis of primary cardiac leiomyosarcoma in a Latin American patient

Primary cardiac malignancies are rare entities. Although sarcomas enclosed the main group of malignant heart neoplasms, primary cardiac leiomyosarcomas are extremely rare and constitutes less than 8% of cardiac tumors. Leiomyosarcoma usually originates from the pulmonary veins and have a worm-like shaped structure. In this article, we present a case of a 40-year-old Hispanic man diagnosed with a cardiac tumor who underwent surgical resection, during pathological examination the tissue samples were consistent with a malignancy of mesenchymal origin that contained irregular bundles of spindle cells. Subsequent immunohistochemical study categorized the mass as a primary heart leiomyosarcoma with positive smooth muscle actin and muscle specific actin. As usual in this type of malignancy, patient’s clinical status declined overtime, recurrence was diagnosed two months after surgery, and four months after the procedure the patient was discharge for palliative care

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