Role of Notch signaling in the mammalian heart

Notch signaling is an evolutionarily ancient, highly conserved pathway important for deciding cell fate, cellular development, differentiation, proliferation, apoptosis, adhesion, and epithelial-to-mesenchymal transition. Notch signaling is also critical in mammalian cardiogenesis, as mutations in this signaling pathway are linked to human congenital heart disease. Furthermore, Notch signaling can repair myocardial injury by promoting myocardial regeneration, protecting ischemic myocardium, inducing angiogenesis, and negatively regulating cardiac fibroblast-myofibroblast transformation. This review provides an update on the known roles of Notch signaling in the mammalian heart. The goal is to assist in developing strategies to influence Notch signaling and optimize myocardial injury repair.

Particulate bioglass in the regeneration of alveolar bone in dogs: clinical, surgical and radiographic evaluations

Bone loss, either by trauma or other diseases, generates an increasing need for substitutes of this tissue. This study evaluated Bioglass as a bone substitute in the regeneration of the alveolar bone in mandibles of dogs by clinical, surgical and radiological analysis. Twenty-eight adult dogs were randomly separated into two equal groups. In each animal, a bone defect was created on the vestibular surface of the alveolar bone between the roots of the fourth right premolar tooth. In the treated group, the defect was immediately filled with bioglass, while in the control, it remained unfilled. Clinical evaluations were performed daily for a week, as well as x-rays immediately after surgery and at 8, 14, 21, 42, 60, 90 and 120 days post-operative. Most animals in both groups showed no signs of inflammation and wound healing was similar. Radiographic examination revealed a gradual increase of radiopacity in the region of the defect in the control group. In the treated group, initial radiopacity was higher than that of adjacent bone, decreasing until 21 days after surgery. Then it gradually increased until 120 days after surgery, when the defect became undetectable. The results showed that Bioglass integrates into bone tissue, is biocompatible and reduced the period for complete bone regeneration.

Air pollution effects on myocardial infarction

OBJECTIVE: Myocardial infarction is an acute and severe cardiovascular disease that generally leads to patient admissions to intensive care units and few cases are initially admitted to infirmaries. The objective of the study was to assess whether estimates of air pollution effects on myocardial infarction morbidity are modified by the source of health information. METHODS: The study was carried out in hospitals of the Brazilian Health System in the city of São Paulo, Southern Brazil. A time series study (1998-1999) was performed using two outcomes: infarction admissions to infirmaries and to intensive care units, both for people older than 64 years of age. Generalized linear models controlling for seasonality (long and short-term trends) and weather were used. The eight-day cumulative effects of air pollutants were assessed using third degree polynomial distributed lag models. RESULTS: Almost 70% of daily hospital admissions due to myocardial infarction were to infirmaries. Despite that, the effects of air pollutants on infarction were higher for intensive care units admissions. All pollutants were positively associated with the study outcomes but SO2 presented the strongest statistically significant association. An interquartile range increase on SO2 concentration was associated with increases of 13% (95% CI: 6-19) and 8% (95% CI: 2-13) of intensive care units and infirmary infarction admissions, respectively. CONCLUSIONS: It may be assumed there is a misclassification of myocardial infarction admissions to infirmaries leading to overestimation. Also, despite the absolute number of events, admissions to intensive care units data provides a more adequate estimate of the magnitude of air pollution effects on infarction admissions.

Immunopathologic studies in myocardial biopsies of patients with Chagas' disease and idiopathic cardiomyopathy

Right ventricular endomyocardial biopsies were studied in 30 patients, 15 with myocardiopathy from chronic Chagas'disease and 15 with idiopathic congestive myocardiopathy; five other myocardial samples were taken at necropsies of patients with chronic Chagas' disease. The authors tried to establish by means of direct immunofluorescence techniques whether there were immunoglobulins G, A and M, fibrinogen and C3 complement deposition in the myocardium; only one of these 30 patients exhibited a positive reaction to IgG, it was a patient with idiopathic congestive myocardiopathy. All fragments from patients with Chagas' disease showed no response to any of the fluorescent conjugates. These findings do not support the idea that anti-myoeardial antibodies have pathogenic importance in the evolution of dilated or chagasic myocardiopathies.

Acute myocardial infarction in chronic Chagas' cardiomyopathy: report of two cases with no obstructive coronary artery lesions

This report describes two patients with chronic Chagas' Heart Disease who developed clinical and laboratorial signs of myocardial infarction. Both patients presented sudden oppressive chest pain, without precipitating factor. In the first case, the highest MB-CK value was 65 IU, 22 hours after the beginning of the pain. On the second case, it was 77 IU at 18 hours after the beginning of the pain. In both cases ECG changes suggesting non-transmural infarction were present. The 99mTc PYP myocardial scintigram of the first case was positive. Coronary angiograms performed on the 18th and 9th day, respectively, after the acute infarction did not display obstructive lesions. Possible mechanisms causing myocardial infarction with normal coronary arteries in Chagas' Disease may include: embolic event's, particularly when there is associated congestive heart failure; coronary thrombosis and coronary spasms.

Chronic myocardial damage in experimental T. cruzi infection of a new world primate, Cebus sp. monkey

Eighteen Cebus apella monkeys, (juvenile and adult of both sexes) were inoculated five years ago, with three Trypanosoma cruzi strains (CA1, n = 10; Colombian, n=4 and Tulahuen, n=4), either by conjunctival or intraperitoneal route, once or repeatedly. Parasitological, hematological, serological, enzymatic, radiographic, electro and echocardiographic findings have been peviously published15 and they are similar to those observed in human pathology. The most frequent electrocardiographic alteration was right branch bundle block. Six animals, chosen at random, were sacrificed. Those sacrificed 20 to 25 months post-first inoculation showed focal accumuli of leukocytes with myocytolysis. Foci of diffuse interstitial fibrosis with mild infiltrate of leukocytes among fibers were observed in the animals sacrificed 36 to 47 months post-inoculation. No parasites were seen. The lesions were more prominent in the ventricular walls and the septum. The fact that the infiltrates were predominant in the animals sacrificed at a shorter time after first inoculation and that fibrosis was more severe in those sacrificed at a longer time suggests that there is a progression of the infiltrative lesions to fibrosis, with a leukocytic activity indicative of a chronic phase. These lesions are similar to those described in human chronic Chagas' disease. This would demonstrate that this model is useful in evaluating a progress in the knowledge of the pathogenesis which is still a controversial issue, immunology, immunogenesis and chemotherapeutic agents of the chronic and indeterminate phases of this disease.

Hepatic regeneration after partial hepatectomy in mice infected with Schistosoma mansoni, at the acute and chronic phases of the disease

Outbred male albino mice normal or infected with 30 cercariae of Schistosoma mansoni (LE strain) were submitted to 65% hepatectomy during the acute (70 days) and chronic phase (160 days) phases of the disease. A group of the infected animals was treated with 400 mg/kg of oxamniquine during the acute phase before hepatectomy. Non-infected, infected and treated but not hepatectomized animals were kept as controls. Hepatic regeneration was evaluated by incorporation of tritiated thymidine, intraperitoneally injected into non-hepatectomized and hepatectomized animals, 24 hours after surgery. The results showed that removal of 65% of the hepatic parenchyma, during the acute phase, led to a statistically significant increase of thymidine incorporation, when compared with the uninfected hepatectomized controls. This phenomenon was not observed at the chronic phase. Treatment with oxamniquine administered during the acute phase led to a decrease in thymidine incorporation rate 160 days after infection (90 days after treatment) and 24 hours after hepatectomy. The data suggest that infection with S. mansoni represents a considerable stimulus for the regenerative capacity of the liver during the acute, but not the chronic phase of disease.

Infectious agents in coronary atheromas: a possible role in the pathogenesis of plaque rupture and acute myocardial infarction

In this review we report our recent findings of histopathological features of plaque instability and the association with Mycoplasma pneumoniae (MP) and Chlamydia pneumoniae (CP) infection, studying thrombosed coronary artery segments (CAS) of patients who died due to acute myocardial infarction. Vulnerable plaques are known to be associated with fat atheromas and inflammation of the plaque. Here we demonstrated that vulnerability is also related with focal positive vessel remodeling that maintains relatively well preserved lumen even in the presence of large atheromatous plaques. This phenomena may explain why the cinecoronariography may not detect large and dangerous vulnerable plaques. Greater amount of these bacteria in vulnerable plaques is associated with adventitial inflammation and positive vessel remodeling: the mean numbers of lymphocytes were significantly higher in adventitia than in the plaque, good direct correlation was obtained between numbers of CD20 B cells and numbers of CP infected cells in adventitia, and between % area of MP-DNA in the plaque and cross sectional area of the vessel, suggesting a cause-effect relationship. Mycoplasma is a bacterium that needs cholesterol for proliferation and may increase virulence of other infectious agents. In conclusion, co-infection by Mycoplasma pneumoniae and Chlamydia pneumoniae may represent an important co-factor for plaque instability, leading to coronary plaque thrombosis and acute myocardial infarction, since larger amount of these bacteria strongly correlated with histological signs of more vulnerability of the plaque. The search of CMV and Helicobacter pilori in these tissues resulted negative.

Effect of hyperbaric oxygen on the regeneration of experimental crush injuries of nerves

Hyperbaric oxygen has been successfully used on treatment of acute ischemic injuries involving soft tissues and chronic injuries. In nerve crush injuries, the mechanisms involved are very similar to those found in ischemic injuries. Consequently, it is logical to hypothesize that hyperbaric oxygen should improve nerve repair, which is a critical step on functional recovery. In the present study, we created standard nerve crush injuries on sciatic nerves of rats, which underwent treatment with hyperbaric oxygen. Results were assessed by functional evaluation using walking-track analysis. The functional recovery indexes observed did not differ from control group. We concluded that hyperbaric oxygen therapy, in the schedule used, had no influence on functional recovery after nerve crush injuries.

Acute pleuropulmonary complications detected by computed tomography following myocardial revascularization

INTRODUCTION: Pleuropulmonary changes are common following coronary artery bypass grafting surgery performed with a saphenous vein graft, with or without an internal mammary artery. The presence of atelectasis or pleural effusions reflects the thoracic trauma. PURPOSE: To define the postoperative incidence of changes in the lung and in the pleural space and to evaluate the influence of the trauma. METHODS: Thirty patients underwent elective coronary artery bypass grafting surgery (8 saphenous vein grafts and 22 saphenous vein grafts and internal mammary artery grafts with pleurotomy). Chest tubes in the left pleural space were used in all internal mammary artery patients. On the second (day 2) and seventh (day 7) postoperative day, patients underwent a computed tomography, and pleural effusions were rated as follows: grade 0 = no fluid to grade 4 = fluid in more than 75% of the hemithorax. Atelectasis was rated as follows: laminar = 1, segmental = 3, and lobar = 10 points. RESULTS: All patients had pleural effusion or atelectasis. Between day 2 and day 7, the number of patients with effusions or atelectasis on the right side decreased (P < 0.05). The incidence of effusions on day 2 in the saphenous vein graft group (87.5%) was higher (P < 0.05) than in the internal mammary artery group (52.3%). The incidence of atelectasis in the lower right lobe decreased (P < 0.05) from 86.7% (day 2) to 26.7% (day 7). The degree of atelectasis in both sides did not differ on day 2 (P = 0.42) but did on day 7 (P < 0.0001). There was a decrease in the atelectasis from day 2 to day 7 on the right side (P < 0.001), but not on the left (P = 0.21). On day 2 there was a relationship between atelectasis and effusion on the right (P = 0.04), but not on the left (P = 0.113). CONCLUSION: The present series demonstrates that there is a high incidence of both minimal pleural effusion and atelectasis after coronary artery bypass grafting surgery, which drops on the right side from day 2 to day 7 post surgery. Factors that contribute to the persistence of changes on the left side include the thoracic trauma and the presence of chest tubes and pericardial effusion.

Parosteal osteosarcoma with myocardial metastasis 13 years after follow-up

PURPOSE: To report the case of a woman with a diagnosis of grade II (low grade) parosteal osteosarcoma with the occurrence of myocardial metastasis 13 years after resection, and to present a review of the existing literature on the subject. METHODS: Description of the case and review of the literature. CONCLUSION: The review leads to the conclusion that the occurrence of metastasis from parosteal osteosarcoma can occur in up to 38% of the cases, in spite of its relatively low aggressiveness. However, myocardial metastasis of a parosteal osteosarcoma is an event that was not found in the literature.

Levels of leaf Herbivory in Amazonian trees from different stages In forest regeneration

Leaves from 120 canopy trees and 60 understory tree saplings growing in primary and secondary forests near Manaus, Brazil, were collected for determination of standing levels of herbivory (percent leaf area lost). Overall, levels of herbivory on leaves of central Amazonian trees were low. About one quarter of the leaves examined (n = 855) had no damage at all. In most other Neotropical sites studied the mean percentage of herbivory was found to vary between 5.7 and 13.1%, whereas in Manaus it was only 3.1%. The data presented here support the contention that levels of herbivore damage are positively related to soil fertility. No significant difference was found in herbivory levels between canopy trees and understory saplings. Also, there was no difference in damage between leaves from pioneer and late successional trees. Field assays of preference, however, revealed that leaves from pioneer trees are more palatable to leaf-cutting ants (Atta laevigata). This effect was dependent upon leaf age, being observed in mature leaves, but not in young leaves. The greater rate of leaf production in secondary forests may be a factor accounting for the greater abundance of leaf-cutting ants in secondary compared to primary forests.

Environmental determinants for natural regeneration of gallery forest at the Cerrado/Amazonia boundaries in Brazil

Natural regeneration and structure and their relationship to environmental variables were studied in three sections of a gallery forest, in Eastern Mato Grosso, Brazil (14º43′S and 52º21′W). The assumption was that natural regeneration is constrained by environmental determinants at all stages of development of the tree community. The objective was to analyse the forest structure and to verify the relationship between species distribution and abundance at different stages of regeneration and environmental variables. In each section, 47 contiguous (10x10m) permanent plots were established to sample trees (gbh≥15cm), following a systematic design. Seedlings (0.01 to 1m height), saplings (1.01 to 2m) and poles (from 2.01m height to gbh<15cm) were sampled in sub-plots of 1x1m, 2x2m and 5x5m, respectively. In each plot, soil properties, gaps projection, bamboos, rocky cover, declivity and depth of ground watertable were determined. The relationships between the environmental variables with trees and seedling communities were assessed by canonical correspondence analysis. In spite of the sections being near to each other, they presented large differences in floristics, structure and site conditions. The forest soil presented a low cation exchange capacity and a high level of Al saturation. The occurrence of bamboos and gaps and the depth of ground watertable limited the occurrence of poles and trees. The high degree of structural heterogeneity for each regeneration category was related primarily to a humidity gradient; but soil fertility (Ca+Mg) was also a determinant of seedling and sapling communities.

Comparative study for the identification of myocardial ischemia by contrast ventriculography under the effect of isosorbide mononitrate and by perfusional myocardial scintigraphy in patients with ischemic heart disease

OBJECTIVE: To evaluate and compare the usefulness of cineventriculographies, before and after nitrate use, to technetium-99m sestamibi scintigraphy for the identification of myocardial ischemia. METHODS: Twenty-six patients were studied at basal conditions and 5 minutes after intravenous administration of isosorbide mononitrate (0.3mg/kg), to evaluate the performance and regional wall motion of the left ventricle (LV). The results were compared to those obtained with technetium-99m sestamibi scintigraphy. RESULTS: Before nitrate, contrast ventriculography identified 30 normal segments, 62 hypokinetic segments, 28 dyskinetic segments, and 14 akinetic segments. After drug administration, 99 segments were normal, 11 hypokinetic, 11 dyskinetic, and 13 akinetic. Myocardial scintigraphy revealed 110 ischemic segments and 18 fibrotic segments (p<0.005). After drug administration, the ventriculography showed increase in the velocity of circumferential fiber shortening (p=0.0142), the ejection fraction (p=0.0462), decrease in the end-systolic volume (p=0.0031) and no change in end-diastolic volume. CONCLUSION: Contrast ventriculography using nitrate proved to be similar to perfusional myocardial scintigraphy in the identification of myocardial ischemia.