The Influence of IL-11 on Cardiac Fibrosis in Experimental Models: A Systematic Review.

Fibrosis is one of the main factors that impair the function of many organs. In the heart, fibrosis leads to contractile dysfunction and arrhythmias, which are important in the development of heart failure. Interleukin (IL)-11 is regulated in various heart diseases and has recently been reported to be an important cytokine in fibrosis in this organ. However, this topic has been little explored, and many questions persist. Thus, this systematic review aimed to report on possible IL-11 therapies evaluated in rodent model-induced cardiac fibrosis. Inclusion criteria were experimental in vivo studies that used different rodent models for cardiac fibrosis associated with IL-11 interventions, without year and language restrictions. The search in PubMed, Web of Science, and Embase databases was performed in October 2022. The risk of bias assessment of the studies was based on the guidelines of the SYRCLE tool, and data from the selected articles were also presented in a table as a narrative description. This review was based on eight studies in which five different interventions were used: recombinant human IL-11 (rhIL-11), anti-IL11 (X203), recombinant mouse IL-11 (rmIL-11), lentivirus (LV)-IL-11 + lutein, and anti-IL11RA (X209). Based on the included studies, the results were variable, with IL-11 overexpression inducing cardiac fibrosis, while inhibition protected against this process, preserving the function of this organ. Therefore, IL-11 stands out as a promising therapeutic target for cardiac fibrosis. However, further studies are needed to understand the mechanisms triggered by each treatment, as well as its safety and immunogenicity.

The Colombian Strain of Trypanosoma cruzi Induces a Proinflammatory Profile, Neuronal Death, and Collagen Deposition in the Intestine of C57BL/6 Mice Both during the Acute and Early Chronic Phase.

The objective of this study was to evaluate the histopathological changes caused by infection with the Colombian strain of Trypanosoma cruzi (T. cruzi) in the acute and chronic experimental phases. C57Bl/6 mice were infected with 1000 trypomastigote forms of the Colombian strain of T. cruzi. After 30 days (acute phase) and 90 days (early chronic phase) of infection, the animals were euthanized, and the colon was collected and divided into two parts: proximal and distal. The distal portion was used for histopathological analysis, whereas the proximal portion was used for quantification of pro- and anti-inflammatory cytokines. In addition, the weight of the animals and parasitemia were assessed. The infection induced gradual weight loss in the animals. In addition, the infection induced an increase in interferon gamma (IFNγ) and tumor necrosis factor-alpha (TNF-α) in the intestine in the acute phase, in which this increase continued until the early chronic phase. The same was observed in relation to the presence of intestinal inflammatory infiltrates. In relation to interleukin (IL)-10, there was an increase only in the early chronic phase. The Colombian strain infection was also able to induce neuronal loss in the myenteric plexus and deposition of the collagen fibers during the acute phase. The Colombian strain of T. cruzi is capable of causing histopathological changes in the intestine of infected mice, especially in inducing neuronal destructions. Thus, this strain can also be used to study the intestinal form of Chagas disease in experimental models.

Biomarkers and Their Possible Functions in the Intestinal Microenvironment of Chagasic Megacolon: An Overview of the (Neuro)inflammatory Process.

The association between inflammatory processes and intestinal neuronal destruction during the progression of Chagasic megacolon is well established. However, many other components play essential roles, both in the long-term progression and control of the clinical status of patients infected with Trypanosoma cruzi. Components such as neuronal subpopulations, enteric glial cells, mast cells and their proteases, and homeostasis-related proteins from several organic systems (serotonin and galectins) are differentially involved in the progression of Chagasic megacolon. This review is aimed at revealing the characteristics of the intestinal microenvironment found in Chagasic megacolon by using different types of already used biomarkers. Information regarding these components may provide new therapeutic alternatives and improve the understanding of the association between T. cruzi infection and immune, endocrine, and neurological system changes.

Cardiac Chagas Disease: MMPs, TIMPs, Galectins, and TGF-ß as Tissue Remodelling Players.

A century after the discovery of Chagas disease, studies are still needed to establish the complex pathophysiology of this disease. However, it is known that several proteins and molecules are related to the establishment of this disease, its evolution, and the appearance of its different clinical forms. Metalloproteinases and their tissue inhibitors, galectins, and TGF-ß are involved in the process of infection and consequently the development of myocarditis, tissue remodeling, and fibrosis upon infection with Trypanosoma cruzi. Thus, considering that the heart is one of the main target organs in Chagas disease, knowledge regarding the mechanisms of action of these molecules is essential to understand how they interact and trigger local and systemic reactions and, consequently, determine whether they contribute to the development of Chagas' heart disease. In this sense, it is believed that the inflammatory microenvironment caused by the infection alters the expression of these proteins favoring progression of the host-parasite cycle and thereby stimulating cardiac tissue remodeling mechanisms and fibrosis. The aim of this review was to gather information on metalloproteinases and their tissue inhibitors, galectins, and TGF-ß and discuss how these molecules and their different interrelationships contribute to the development of Chagas' heart disease.

Morphometric evaluation of the aortic root in stillborns.

OBJECTIVE: To describe the dimensions and amount of collagen in the aortic root of autopsied fetuses at different gestational ages. MATERIAL AND METHODS: 40 samples of aortic roots were selected from autopsied fetuses with gestational ages ranging between 20 and 40 weeks. The thickness and the area of the aortic wall were analyzed on slides stained with Hematoxylin and Eosin, and the collagen was quantified on slides stained with Picrosirius, by using an image analyzing system. RESULTS: A positive correlation was observed between the thickness of the media layer of the aortic wall and the gestational age. There was a positive and significant correlation between the percentage of collagen in the aortic wall with gestational age and fetal weight. The correlation between gestational age and the area of the aortic root circumference was positive and significant. And the correlation between the aortic diameter and the gestational age as well as fetal length was positive and significant. CONCLUSION: The thickness of the media layer, the amount of collagen in the aortic wall, the area of the aortic root circumference and the aortic diameter rose with the increase of the gestational age. Thus, the morphological analysis of the aortic root may help as a parameter during the follow-up of inter-uterine growth and fetal development.

Influence of AIDS in collagen deposition and thickness of the bone marrow.

Bone marrow abnormalities are frequently observed in individuals with AIDS. Dysplasia, the most common abnormality, is found in more than 50% of patients infected with the HIV. The aim of this study was to assess trabecular thickness and collagen content as well as cellularity in the bone marrow of patients with AIDS. Sixty bone marrow samples were collected from the sternum of autopsied patients with or without AIDS (n = 30, each). Cellularity and trabecular thickness was assessed by performing hematoxylin-eosin staining; picrosirius staining was used to evaluate collagen content. Morphometric analyses were performed by using a Zeiss KS300 system (Kontron-Zeiss). Patients with AIDS showed a significant reduction in trabecular bone thickness and an increase in collagen deposition. No statistically significant differences were observed in cellularity between the 2 groups. Therefore, reduced thickness and increased collagen deposition were observed in the trabeculae of the bone marrow of patients with AIDS due to possible interaction between cytokines and bone marrow components.

Clinical and epidemiological prevalence of glomerulopathies elderly in the city of Uberaba - MG.

INTRODUCTION: Currently, the elderly population of Brazil is suffering significant increase. Aging is a physiological process that causes changes in various organs, including the kidney. A kidney biopsy is of paramount importance to clarify the morphological changes of these entities. OBJECTIVES: The aim of this work was to conduct a clinical epidemiological analysis of elderly patients and evaluate the prevalence of major glomerulopathies that affect. METHODS: This is a retrospective and descriptive, with a review of 104 reports of renal biopsies of elderly aged over 60 years, performed in the Nefropatologia Federal University of Triângulo Mineiro (UFTM), between periods January 1996 and December 2010. Patients were grouped according to clinical syndrome. RESULTS: We reviewed 104 biopsies of elderly patients. Of these, 52.94% were male. The Hypertension was found in 50.54% of patients. The clinical syndrome was the predominant nephrotic syndrome (42.17%). Most disease was glomerular origin. The glomerulopathy was the most prevalent (34.07%). DISCUSSION/CONCLUSION: Through this review, we noted that the nephrotic syndrome was the main clinical syndrome and Podocytophaties glomerulopathies were more prevalent in the group of elderly patients undergoing renal biopsy. The analysis of renal biopsies of elderly patients is of paramount importance, since knowledge of the clinical manifestations of major glomerulopathies that affect this group, to assist in establishing the diagnosis and therapeutic management.

The relation between FoxP3⁺ regulatory T cells and fungal density in oral paracoccidioidomycosis: a preliminary study.

Regulatory T (Treg) cells may play an important role in the pathogenesis of paracoccidioidomycosis (PCM), but data on the role of Treg cells in the context of oral PCM are still scarce. The objectives of this study were to investigate the density of FoxP3(+) T regulatory cells in oral PCM and to correlate the results with the density of Paracoccidioides brasiliensis in the lesions. Cases of chronic oral PCM seen between 2000 and 2008 were included in this study. The diagnosis of all lesions was confirmed with histopathological examination and Grocott-Gomori staining. The quantitative analysis of the viable fungi was conducted in all cases with Grocott-stained slides. Treg cells were identified using antibodies against FoxP3. Pearson correlation coefficient was used to test the correlation between the density of fungi and Treg cells. Results were considered significant when P < 0.05. A total of 11 cases of oral PCM were obtained. There was a positive correlation between fungal density and FoxP3(+) Treg cells density in oral lesions, however, without statistical significance. A positive relation between Treg cells and fungal density was seen in oral PCM. Further studies are required to further elucidate the role of these cells in the pathogenesis of oral PCM, as well the clinical significance of these findings.

Role of mast cell chymase and tryptase in the progression of atherosclerosis: study in 44 autopsied cases.

The aim of this study was to describe the role of mast cell chymase and tryptase in the progression of atherosclerosis. Forty-four sections of aortas were obtained from autopsies. We assessed the macroscopic degree of atherosclerosis, microscopic intensity of lipid deposition in the tunica intima, percentage of collagen in the tunica intima, and density of immunostained mast cells. There was no significant difference between the density of mast cell tryptase and chymase concerning ethnicity, sex, cause of death, or degree of atherosclerosis. The density of mast cell chymase was significantly higher in the nonelderly group. The percentage of collagen was significantly higher in elderly patients. There was a positive and significant correlation between the degree of macroscopic atherosclerosis and lipidosis, the density of mast cell chymase and the percentage of collagen, the density of mast cell tryptase and the percentage of collagen, and lipidosis and the density of mast cell tryptase. The degree of macroscopic lesion of atherosclerosis increased proportionally with the increase in the density of mast cell chymase and tryptase and in the intensity of lipid deposition and with the percentage of collagen in the atherosclerotic plaques. Thus, mast cells may play a crucial role in aggravating atherosclerotic lesions.

Causes of death in older people autopsied.

Studies of causes of death in autopsied older people are not common in Brazil. The aims were to compare demographic data and causes of death in elderly people autopsied in the 1970s, 1980s, and 1990s and to relate causes of death to age, sex, color, and body mass index. Data survey of the autopsy reports came from the Hospital de Clínicas of the Universidade Federal do Triângulo Mineiro, Uberaba, Minas Gerais, Brazil. The data were obtained from the autopsied individuals 60 years or older. Median age was 69 years (60-120 years) and was higher in the 1990s than in the 1970s (70.5 vs 68.0, P < .05) and higher in women (70 vs 68 years, P < .05). Men (66.8%) and white people (70.0%) predominated during the period. The most frequent causes of death were cardiovascular (42%) and infectious (33.4%). The percentage of cardiovascular causes of death varied little over the 1970s (41.7%), 1980s (42.3%), and 1990s (42.9%), whereas that of infectious causes decreased (38.0%, 28.6%, and 28.6%, respectively) and that of neoplastic causes increased (10.3%, 12.6%, and 19.6%, respectively, P > .05). Most of the elderly (84.6%) presented a body mass index of less than 22 kg/m2 and malnutrition predominated in the 1980s (48%). Therefore, there was little percentage variation in cardiovascular-related deaths over the 3 decades while the percentage of neoplastic-related deaths increased. Infectious causes of death was associated with the lowest body mass index, and the greatest percentage of cardiovascular and neoplastic-related deaths were in women.

Salivary gland tumor: a review of 599 cases in a Brazilian population.

Salivary gland tumors consist of a group of heterogeneous lesions with complex clinicopathological characteristics and distinct biological behaviors. Worldwide series show a contrast in the relative incidence of salivary gland tumors, with some discrepancies in clinicopathological data. The main aim of this study was to describe demographic characteristics of 599 cases in a population from Central Brazil over a 10-year period and compare these with other epidemiological studies. Benign tumors represented 78.3% of the cases. Women were the most affected (61%) and the male:female ratio was 1:1.6. Parotid gland tumors were the most frequent (68.5% of cases) and patient age ranged from 1 to 88 years-old (median of 45 years old). The most frequent tumors were pleomorphic adenomas (68.4%) and benign tumors were significantly more frequent in the parotid (75.9%), while malignant tumors were more frequent in the minor salivary glands (40%) (P < 0.05). In conclusion, women and the parotid gland were the most affected and pleomorphic adenoma was the most frequent lesion, followed by adenoid cystic carcinoma and Warthin's tumor.

Macroscopic aspects of chronic Chagas heart disease in aging.

OBJECTIVE: To describe the macroscopic characteristics of chronic Chagas heart disease in autopsied elderly. METHODS: The elderly studied were 60 or older. Twenty of them had chronic Chagas heart disease (CHD) and positive serology for the disease, and 14 had no heart disease (WHD) nor morphological changes suggestive of it and were serologically negative for Chagas disease. RESULTS: The CHD elderly had cardiac weight greater than the WHD (385 +/- 141.1 vs 306.8 +/- 62.1g, respectively; p > 0.05), in addition to significantly higher heart weight-to-body weight ratio (0.71% [0.5-1.42%] vs 0.59% [0.47-0.91%] p < 0.05). When compared, the CHD elderly presented lower fibrous thickening and/or atherosclerosis in the ascending aorta, mitral and tricuspid valves, and left and right coronaries than the WHD elderly. In the aortic and mitral valves, the lesions were significantly less severe (p < 0.05). Left ventricular apical lesion was observed in 45% of the CHD elderly, and intracardiac thrombosis in the left ventricle was found in 10% of them. CONCLUSION: Fibrous thickening and/or atherosclerosis were found to be less severe in the valves and arteries of the CHD elderly. Moreover, heart weight and intracardiac thrombosis frequency were lower than those detailed in the literature for non-elderly individuals.

Cerebral and cardiac amyloidosis in autopsied elderly individuals.

INTRODUCTION: Amyloidosis in elderly individuals can be an independent alteration and a characteristic of aging. However, the clinical, pathophysiologic, and biochemical characteristics of amyloidosis related to age remain uncertain. OBJECTIVE: The purpose of this study was to determine the extent to which the heart and/or the brain of individuals aged 60 years or over exhibits amyloid deposits. MATERIALS AND METHODS: The autopsy findings of individuals who were at least 60 years old were studied. The autopsies took place between the years of 1976 and 2000. A total of 10 cases were selected that had hearts without cardiopathies, had negative serology for Chagas' disease, and had brains without morphological changes related to encephalopathies. Slides with fragments of heart and brain were processed and analyzed using polarized and common light microscopy. RESULTS: Of the 10 cases, 4 were positive for amyloidosis. All had positive findings in the brain, and 1 case also had positive findings in the heart. Among the positive cases, 50% were of people aged 60 to 69 years. There appeared to be a relationship between the presence of amyloid deposits and the ratio of brain and body weight, with the ratio in the positive cases being smaller than in the negative cases. CONCLUSIONS: The analysis of amyloid deposits in the brains and hearts of elderly individuals shows that such deposits may lead to a systemic attack of senility, common to natural aging. It is not certain that beta-amyloid deposits would alone bring such drastic repercussions to the individual. Some additional disorders of the organism could cause the breakdown of the natural balance related to the accumulation of these proteins, leading the way to the pathological contexts of amyloidosis.

[Infeccious diseases as causes of death in autopsied elderly]. / Doenças infecciosas como causas de morte em idosos autopsiados.

The population aging in Brazil was associated with the alterations in the morbimortality of the population. The aim of this study was to verify the causes of death and other pathological processes in autopsied elderly. The elderly with 60 years or more in the period from 1976 to 1998 represented 394 cases (24.4%). The age median was 69 years ranged from 60 to 120 years, being higher in the women (70.5 versus 68 yrs;p<0.05). The male gender (67.5%), white color (69.8%), and the cardiovascular (43.7%) and infectious (31%) causes of death were dominate. In the malnourished (76.2%) it had association of pneumonia and cystitis, (p<0.05). Arteriosclerosis (61.9%), and the chagasic (42.1%) and hypertensive cardiopathies (39.1%) were the most frequent processes. Therefore, it was observed an overlapping of chronic-degenerative and infectious causes of death. This study shows the necessity to value of follow up of body mass index and of risk factors for the development of illness in aging patients like pneumonia.