Morphological and histopathological evaluation of autopsied patients with hypertensive cardiopathy.

BACKGROUND: Physiopathological processes in hypertensive heart disease are controlled by complex interactions between cardiomyocytes, extracellular matrix, microvasculature and other cells present in the myocardium. OBJECTIVE: To analyze morphological changes in hypertensive cardiopathy and to describe and compare findings in order to help clarify determinant factors. METHODS: 42 fragments of the left ventricular myocardium and circumflex branch of the left coronary artery were obtained from individuals autopsied at the Clinical Hospital of the Federal University of Triângulo Mineiro (UFTM) in the period ranging from 1984 to 2018. Groups were split into individuals with hypertensive heart disease (HD) and individuals without heart disease (ND). Wall thickness was measured with a digital caliper and Computed Tomography. Quantification of collagen fibers was conducted by computerized morphometry and mast cell density was assessed by immunohistochemical methods. RESULTS: There was a significant increase of heart weight in the HD group compared to the ND group, (p = 0.0002). There was a significant increase of thickness of the middle third of the free wall in the HD group compared to the ND group, (p = 0.04). There was a significant increase of collagen fibers in the left ventricle in the HD group compared to the ND group, (p < 0.0001). Concerning mast cell density, there was a significant increase in the left ventricle of individuals with HD immuno-labeled by the set anti-chymase/anti-tryptase (p < 0.0001). There was a significant increase of mast cell density in the circumflex branch of the left coronary artery of individuals with HD immuno-labeled by the set anti-chymase/anti-tryptase (p = 0.01). CONCLUSIONS: Mast cells are involved in the development of hypertensive heart disease, contributing to the remodeling of collagen fibers in this disease.

Melatonin treatment in fetal and neonatal diseases.

This literature review aims to address the main scientific findings on oxidative stress activity in different gestational disorders, as well as the function and application of melatonin in the treatment of fetal and neonatal changes. Oxidative stress has been associated with the etiopathogenesis of recurrent miscarriages, preeclampsia, intrauterine growth restriction, and stillbirth. Both, the exacerbated consumption of the antioxidant enzymes superoxide dismutase, catalase and glutathione peroxidase, and the increased synthesis of reactive oxygen species, such as superoxide, peroxynitrite, and hydrogen peroxide, induce phospholipid peroxidation and endothelial dysfunction, impaired invasion and death of trophoblast cells, impaired decidualization, and remodeling of maternal spiral arteries. It has been postulated that melatonin induces specific biochemical responses that regulate cell proliferation in fetuses, and that its antioxidant action promotes bioavailability of nitric oxide and, thus, placental perfusion and also fetal nutrition and oxygenation. Therefore, the therapeutic action of melatonin has been the subject of major studies that aim to minimize or prevent different injuries affecting this pediatric age group, such as intrauterine growth restriction, encephalopathy, chronic lung diseases, retinopathy of prematurity Conclusion: the results antioxidant and indicate that melatonin is an important therapy for the clinical treatment of these diseases.

Skin aging in patients with acquired immunodeficiency syndrome.

To evaluate the histomorphometric skin changes over aging patients with autopsied acquired immunodeficiency syndrome (AIDS). In 29 skin fragments of autopsied elderly (older than 50 years) and nonelderly patients with AIDS, epidermal thickness, the number of layers, the diameter of cells, the percentage of collagen and elastic fibers in the dermis, and the number and morphology of Langerhans cells were assessed. Statistical analysis was performed by SigmaStat 2.03 program. The thickness of the epidermis (92.55 × 158.94 µm), the number of layers (7 × 9 layers), and the diameter of the cells (13.27 × 17.6 µm) were statistically lower among the elderly. The quantity of collagen fibers (9.68 × 14.11%) and elastic fibers (11.89 × 15.31%) was also significantly lower in the elderly. There was a decrease in total (10.61 × 12.38 cel/mm(2)) and an increase in immature Langerhans cells (6.31 × 4.98 cel/mm(2)) in elderly patients with AIDS. The aging of the skin of patients with AIDS is amended in different histomorphometric aspects, the epidermis constituents suffer less pronounced changes in normal aging, and the dermis has more intense changes in elastic fibers and collagen.

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.

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.

The influence of gender and of AIDS on the immunity of autopsied patients' esophagus.

Previous studies have shown that males who have AIDS are more frequently affected by infectious diseases than females. The esophagus is the organ in the digestive tube that is more commonly affected by opportunistic infections during the syndrome. The aim of this study was to assess the influence of AIDS and of gender on local immunity of the esophageal epithelium. Fragments of the esophagus from 29 autopsied women and 37 autopsied men were collected at a university hospital from 1980 to 2009 and were divided in groups with and without AIDS. The IgA-, IgG-, and IgM-positive cells and Langerhans cells (LCs) were immunostained, respectively, with anti-IgA, anti-IgG, anti-IgM, and anti-S100. The software Image J was used to measure the esophageal epithelium and to count the epithelium cellular layers. Patients with AIDS, apart from gender, showed an increase in IgA-, IgG-, and IgM-positive cells and a reduction of Langerhans cells, in thickness and in number of cellular layers in the esophageal epithelium. However, among individuals with AIDS, men presented lower secretory expression of IgA-, IgG-, and IgM-positive cells than women and more intense reduction of LCs. Women have naturally presented better local esophageal immunity than men. Although AIDS possibly causes immunological and morphological alterations in the esophageal epithelium in both genders, women have better esophageal immunity, which may explain a greater frequency of hospital admissions due to infection of men with AIDS when compared with women.

Analysis of placenta vascularization in patients with uterine altered artery Doppler flow velocity exams.

BACKGROUND: One of the frequent questions in obstetric practice is to determine placental vascular changes that may account for abnormal Doppler flow velocity alterations in maternal uterine vessels from women and fetuses without pregnancy pathology. METHODS: A retrospective morphometric study was realized using 27 placentas from patients submitted for Doppler flow velocity exam during pregnancy. The placentas were morphologically examined using hematoxylin-eosin staining. Measurements of villi were made with the use of a video camera coupled to a common light microscope and a computer with automatic image analyzing software. RESULTS: Of the 27 placentas, 13 (48%) were of patients showing unaltered Doppler and 14 (52%) showing altered Doppler. The number of stem villi vessels was significantly larger in the placentas of patients with Doppler exam alterations (P = 0.003). This group also presented greater stem villi vessel thickness, although without significant difference. The number of intermediary and terminal villi vessels was greater in the placentas of patients with altered Doppler exams (P < 0.001), and a greater terminal villi area was observed in these cases (P < 0.001). CONCLUSION: The morphological proof that uterine artery Doppler flow velocity exam alterations are associated with placental vascular alterations demonstrates the importance of this exam during prenatal care, even in the absence of maternal-fetal alterations.

A Role for galectin-3 in renal tissue damage triggered by ischemia and reperfusion injury.

Ischemic-reperfusion injury (IRI) triggers an inflammatory response involving neutrophils/macrophages, lymphocytes and endothelial cells. Galectin-3 is a multi-functional lectin with a broad range of action such as promotion of neutrophil adhesion, induction of oxidative stress, mastocyte migration and degranulation, and production of pro-inflammatory cytokines. The aim of this study was evaluate the role of galectin-3 in the inflammation triggered by IRI. Galectin-3 knockout (KO) and wild type (wt) mice were subjected to 45 min of renal pedicle occlusion. Blood and kidney samples were collected at 6, 24, 48 and 120 h. Blood urea was analyzed enzymatically, while MCP-1, IL-6 and IL-1beta were studied by real-time PCR. Reactive oxygen species (ROS) was investigated by flow cytometry. Morphometric analyses were performed at 6, 24, 48 and 120 h after reperfusion. Urea peaked at 24 h, being significantly lower in knockout animals (wt = 264.4 +/- 85.21 mg/dl vs. gal-3 KO = 123.74 +/- 29.64 mg/dl, P = 0.001). Galectin-3 knockout animals presented less acute tubular necrosis and a more prominent tubular regeneration when compared with controls concurrently with lower expression of MCP-1, IL-6, IL-1beta, less macrophage infiltration and lower ROS production at early time points. Galectin-3 seems to play a role in renal IRI involving the secretion of macrophage-related chemokine, pro-inflammatory cytokines and ROS production.

Histochemical and immunohistochemical study of the glomerular development in human fetuses.

Few studies exist that establish the normal morphological patterns of glomerular development, though this is one of the organs that continues to evolve morphologically during the postnatal period up to 4 weeks after birth. In our study one kidney from each autopsy of a total of 86 autopsies was analyzed [15 weeks to 40 weeks of gestational age (GA)]. We examined the variation in the nephrogenic zone thickness, the area and diameter of the glomerular tuft, the area and diameter of the glomerular capsule, and the immunohistochemical markers, anti-CD31 and anti-CD34 antibodies, which accompany the development of the glomerular microvasculature. Periodic acid-methenamine silver (PAMS) stain was used for the morphological and morphometrical analyses, and it was particularly useful in fetuses in which autolysis had occurred. The length of the nephrogenic zone (NZ) decreased with the increase of the GA (P < 0.001) according to the formula: GA = 36.5 - (0.05 x length of NZ). The areas of the Bowman capsule (P < 0.0001), the capillary tuft (P < 0.0001), and the capillary tuft diameter (P = 0.00393) of the intermediary glomeruli increased with the advance of GA, with a positive significant correlation. The same parameters of the juxtamedullary and superficial glomeruli had no correlation with the advance of GA. The cells of the primary structures in the "S" shape of the primitive nephrons were negative for CD31 and CD34. Staining for both antibodies was found, for all GAs, in the endothelial cells of the mature glomeruli tuft and in the renal interstitial vessels. The data obtained in this work contribute to the evaluation of renal maturity in autopsied fetuses and are particularly important in fetuses when autolysis has occurred, to which the parameters used in this study can also be applied. The establishment of normal morphometric and immunohistochemical parameters for the evaluation of renal maturity increases the diagnostic precision of renal pathological alterations in aborted material and perinatal autopsy.

Freqüência de alterações cérvico-vaginais em mulheres submetidas ao exame citopatológico / Frequency of cervico vaginalis alteration in submitted patients of cytopathological exam / Frecuencia de las alteraciones cervicovaginal en mujeres sometidas al examen citopatógico

O Exame citopatológico é o método de triagem que auxilia na detecção precoce do câncer e de lesões pré-cancerosas da cérvix. No Brasil, o câncer cervical representa a segunda neoplasia maligna mais incidente em mulheres. O objetivo desse estudo foi avaliar a freqüência das alterações citopatológicas de acordo com a faixa etária. A seleção dos casos foi realizada através dos resultados dos exames citopatológicos, de mulheres na faixa etária entre 14 a 80 anos, obtidos no Centro de Atenção Integrada à Saúde da Mulher, Uberaba (MG), no período de 2001 a 2003. Dos 35.220 resultados obtidos, em 3,34% foram descritos alterações no epitélio cérvico-vaginal, sendo mais freqüentes as alterações escamosas e glandulares de significado indeterminado (53,7%) e as infecções pelo HPV (31%). As mulheres mais jovens (< 40 anos) foram significativamente mais acometidas por essas alterações (p<0,005). Neoplasias invasivas acometeram 5,6% das mulheres a partir da quarta década de vida (p<0,005). Os diagnósticos das alterações no epitélio cérvico-vaginal de acordo com a faixa etária das mulheres foram semelhantes aos descritos na literatura, sendo que infecção pelo HPV, principal agente potencialmente carcinogênico, acometeu mulheres mais jovens e as neoplasias invasivas foram mais freqüentes a partir da quarta década de vida.

The cytopathological exam is useful recommended for early diagnoses of neoplastic and of pre-neoplastic lesions of the uterine cervix. In Brazil, cervix neoplasm is the second most frequent malignant neoplasm in women. The aim of this study was evaluate the frequency of cytopathologic alterations and its relationship with age. The cases selection was performed by means of cytopathological exam results in women aged 14 to 80 years old, by the revision in Centro de Atenção Integrado a Saúde da Mulher, Uberaba (MG), during the period of 2001-2003. From de 35.220 reviewed exams, 3.34% tests showed alterations in the cervico vaginalis epithelium, with a higher frequency in the squamous cervical epithelium alterations and glandular epithelium alterations of unknown significance (53.7%) as well as infection by the Human Papillomavirus (HPV) (31%). The infections caused by the HPV and atypical glandular and scamous cells of undetermined significance were more frequent in ages under the 40 (p<0.005), yet the occurrence of cervical carcinoma was more frequent in women over 40 (p<0.005). Therefore, the frequency of cytopathologic alterations of the cervical and vaginal epithelium and its relationship to age were resemblance to described in literature. The HPV infection, the best carcinogenic potential agent attacked younger patients and the invasive neoplasm was more frequent in women over 40 years old.

El exámen citopatológico es un método de triage que ayuda a realizar una detección precoz del cáncer y de lesiones pre-cancerosas del cérvix uterino. En el Brasil, el cáncer cervical representa la segunda neoplasia maligna mas incidente en mujeres. El objetivo del estudio fue avaliar la frecuencia de las alteraciones citopatológicas de acuerdo con el grupo etario. La selección de los casos fue realizada a través de los resultados de los exámenes citopatológicos, de mulheres dentro del grupo etario entre 14 a 80 años, obtenidos del Centro de Atención Integrada a la Salúd de la Mujer, Uberaba (MG), durante el período del 2001 al 2003. De los 35.220 resultados obtenidos, en 3,34% fueron descritas alteraciones en el epitélio cervico-vaginal, siendo mas frecuentes las alteraciones escamosas e glandulares de significado indeterminado (53,7%) y las infecciones por el HPV (31%). Las mulheres más jóvenes (<40 años) fueron significativamente más acometidas por esas alteraciones (p<0,005). Así, las neoplasias invasivas acometieron al 5,6% de las mulheres a partir de la cuarta década de vida (p<0,005). Los diagnósticos de las alteraciones del epitélio cérvico-vaginal de acuerdo con el grupo etario de las mulheres fueron semejantes a otros hallazgos ya descritos en la literatura, siendo que la infección por el VPH, principal agente con potencial carcinogénico, acometió a mulheres más jóvenes y las neoplasias invasivas fueron más frecuentes a partir de la cuarta década de vida.

Disseminated toxoplasmosis presenting as sepsis in two AIDS patients.

This report describes two patients who presented acute disseminated and severe toxoplasmosis as the first opportunistic disease related to acquired immunodeficiency syndrome. At admission, clinical and laboratory findings were similar to sepsis or septic shock and a fast evolutive course to death occurred in both cases. At necropsy, an inflammatory reaction and presence of a great number of Toxoplasma gondii cysts and tachyzoites were observed in most organs examined.

Pioglitazone limits cyclosporine nephrotoxicity in rats.

Chronic cyclosporine (CsA) nephrotoxicity is a relevant factor in the pathogenesis of chronic allograft nephropathy. Pioglitazone is an agonist of PPARgamma, capable of reducing chronic inflammation. We investigated the capacity of pioglitazone in preventing renal dysfunction. Adult male Wistar rats were assigned to: Vehicle (olive oil 1 ml/kg/day), CsA (10 mg/kg/day) alone and with pioglitazone (5 or 10 mg/kg/day). The animals were sacrificed at 28 days, where blood (serum creatinine ratio, CR) and kidney samples (arteriolopathy analyses) were collected. The mRNA transcripts of TGF-beta1, PAI-1, Smad3 and 7 were evaluated by real-time PCR. As expected, CsA treatment significantly decreased renal function that peaked at day 28, compared with vehicle (CR=1.29+/-0.03 vs. 0.95+/-0.14, p<0.05). In contrast, the administration of pioglitazone 5 or 10 mg/kg combined with CsA resulted in better renal function (CR=1.09+/-0.05 and 1.14+/-0.14, respectively, p<0.05). Animals treated with CSA showed relevant arteriolopathy (49.5+/-2.86%) and pioglitazone administration significantly limited it (37.0+/-3.59% and 36.6+/-1.72%, respectively, 5 or 10 mg/kg, p<0.05). In CsA-treated animals (alone and with pioglitazone), TGF-beta1 and Smad3 increased significantly. In animals treated with CsA and pioglitazone (5 mg/kg), PAI-1 was significantly lower than CsA alone (3.96+/-0.92 vs. 7.53+/-1.38, p<0.05). Interestingly, the administration of pioglitazone 5 or 10 mg/kg was associated with an increase in Smad7 (1.79+/-0.25 and 1.75+/-0.19, respectively), compared to vehicle and to CsA-treated groups (1.08+/-0.17 and 1.17+/-0.19, respectively, p<0.05). These data provide evidence that pioglitazone acts through down regulation of pro-fibrotic cytokine PAI-1 and overexpression of the regulatory Smad7.

Assessment of renal maturity by assisted morphometry in autopsied fetuses.

BACKGROUND: The kidney is one organ which presents distinct morphology depending on GA; the classic references for kidney measurements were established several years ago and it is not certain if they are still accurate. AIM: To evaluate the renal maturity using a computer-assisted morphometry in autopsied fetuses within 20 to 40 weeks of GA. STUDY DESIGN: Microscopic hematoxylin and eosin stained renal sections from 67 stillborns were utilized for the morphometric analyses. RESULTS: It was possible to promote an adjustment in the formula used to calculate the number of mature glomeruli layers to the GA (GLN = 0.212GA + 0.0169) in autopsy material and it was different from the literature (Sr = 0.709; p < 0.001). Regarding the nephrogenic zone, it decreases with the GA as confirmed by the regression equation NZ = 490.7-(11.9 x GA) (p < 0.001; Sr = -0.685). CONCLUSION: In conclusion, our data contribute to the evaluation of renal maturity and GA in autopsied fetuses, showing particular importance in autolyzed fetuses, in which the parameters used in the present study can still be applied. The correction of the formula for counting mature glomeruli layers for each GA and the addition of new morphometric parameters for the evaluation of renal maturity increase the precision for the analysis of spontaneous abortion and autopsy material, improving the correlation with pathological processes in clinical findings and in the other organs.

Inflammation and glandular duct dilatation of the tongue from patients with chronic Chagas disease.

The purpose of this study was to evaluate morphologically the tongue of individuals with chronic Chagas disease (CD) in comparison to the non-chagasic ones. Twenty-four protocol cases of autopsies were selected. They were subdivided into CD patients (10 cases) and non-chagasic ones (14 cases). The morphometric analysis was accomplished for the tongue muscle and salivary glands duct lumen area. In three CD patients, perineuritis was found, and two of them showed megaesophagus and megacolon. The intensity of the inflammation in the von Ebner's glands, the tongue muscles, and the salivary glands duct lumen area was significantly higher in the CD patients. We concluded that the CD patients show salivary glands duct dilatation, which probably would have a relation with alterations in the autonomic nervous system. The inflammation found in CD patients is in accordance with that described in comparative studies on the digestive tract and heart. These morphological findings suggest that the histopathological analysis of the tongue associated with other organs, or even in an isolated manner, can add in the diagnosis and pathogenesis of the CD chronic phase.