Comparison between the collagen intensity and mast cell density in the lingual muscles and myocardium of autopsied chronic chagasic and nonchagasic patients.

In chronic Chagas' disease (CD), an increase in collagen intensity and mast cell density has been described individually in the myocardium and tongue muscles. The aim of this study was to compare the percentage of collagen, mast cell tryptase (MCT) density, and mast cell chymase (MCH) density in the lingual muscles and myocardium from autopsied chagasic (CP) and nonchagasic patients (NCP). The selected cases were divided into two groups: (1) CP (n = 10) and (2) NCP (n = 10). Fragments were removed from the tongue and heart. After histological processing, the slices were stained with picrosirius, and immunohistochemistry was performed for MCH and MCT. The CP group showed the highest MCH and MCT densities and the highest percentage of collagen in the lingual muscles and myocardium when compared with the NCP group (p < 0.05). A significant positive correlation was observed between the collagen intensity and MCH density in the myocardium of the CP group. Although there are no reports in the literature of MCT and MCH in CD, its higher densities as well as higher percentage of collagen were found in the lingual muscles and myocardium in the CP group, suggesting that tryptase and chymase are associated with the pathogenesis of CD in these organs. Furthermore, the positive and significant correlation between the percentage of collagen and MCH density in the myocardium of the CP group suggests that the chymase is associated with fibrosis in CD, as demonstrated in other diseases.

Expression of cytokines and chemokines and microvasculature alterations of the tongue from patients with chronic Chagas' disease.

Chagas' disease is caused by the protozoan Trypanosoma cruzi and continues to be a significant public health problem, since 10 million people are still infected in Latin America. The purpose of this study was to analyze the microvasculature alterations as well the expression of cytokines and chemokines in the tongues from patients with chronic Chagas' disease (CC; n = 18), comparatively with a non-chagasic group (NC; n = 22). We observed several vascular alterations in the tongue of CC such as a greater vascular diameter, increased vascular wall area, high density of the blood vessels, and increased thickening of the capillary basement membrane. The expression of cytokines interferon gamma and tumor necrosis factor alpha and chemokine macrophage inflammatory protein 1alpha were significantly down-regulated in the tongue of CC group. These results demonstrated that, in the tongue of chagasic patients, a microvascular abnormality and immunological impairment occurs, probably due to chronic inflammation evoked by T. cruzi antigens.

Increased expression and phosphorylation of focal adhesion kinase correlates with dysfunction in the volume-overloaded human heart.

FAK (focal adhesion kinase) has been shown to mediate the hypertrophic growth of the left ventricle. Experimental results also suggest that FAK may contribute to the structural and functional deterioration of the chronically overloaded left ventricle. In the present study, we postulated that FAK expression and phosphorylation may be altered in the volume-overloaded heart in humans. FAK expression and phosphorylation at Tyr(397) were detected by Western blotting and immunohistochemistry in samples from endomyocardial biopsies from patients with MR (mitral regurgitation; n=21) and donor subjects (n=4). Hearts from patients with MR had degenerated cardiac myocytes and areas of fibrosis. In this group, the myocardial collagen area was increased (18% in MR hearts compared with 3% in donor hearts respectively) and correlated negatively with left ventricular ejection fraction (r=-0.74; P>0.001). FAK expression and phosphorylation at Tyr(397) (a marker of the enzyme activity) were increased in samples from MR hearts compared with those from donor hearts (3.1- and 4.9-fold respectively). In myocardial samples from donor hearts, anti-FAK staining was almost exclusively restricted to cardiac myocytes; however, in myocardial samples from MR hearts, staining with the anti-FAK antibody was found to occur in myocytes and the interstitium. There was a positive correlation between collagen and the interstitial areas stained with the anti-FAK antibody (r=0.76; P>0.001). Anti-FAK and anti-vimentin staining of the interstitial areas of samples from MR hearts were extensively superimposed, indicating that most of the interstitial FAK was located in fibroblasts. In conclusion, FAK expression and phosphorylation are increased and may contribute to the underlying structural and functional abnormalities in the volume-overloaded heart in humans.

Dehydroepiandrosterone increases beta-cell mass and improves the glucose-induced insulin secretion by pancreatic islets from aged rats.

The effect of dehydroepiandrosterone (DHEA) on pancreatic islet function of aged rats, an animal model with impaired glucose-induced insulin secretion, was investigated. The following parameters were examined: morphological analysis of endocrine pancreata by immunohistochemistry; protein levels of insulin receptor, IRS-1, IRS-2, PI 3-kinase, Akt-1, and Akt-2; and static insulin secretion in isolated pancreatic islets. Pancreatic islets from DHEA-treated rats showed an increased beta-cell mass accompanied by increased Akt-1 protein level but reduced IR, IRS-1, and IRS-2 protein levels and enhanced glucose-stimulated insulin secretion. The present results suggest that DHEA may be a promising drug to prevent diabetes during aging.

Description of microscopic lesions of vestibular folds of autopsied adults and their relationship with cause of death and underlying disease.

UNLABELLED: The increase in invasive methods currently applied to diagnosis airway upper tract infection leads to a possible increase in vestibular folds (VF) lesions. Besides, VF importance in the prevention of the organism against infection pathogens had been stressed and few studies had addressed the microscopic lesions of the VF in autopsied patients because there is no routine VF examination in the postmortem exam. AIM: The aim of this study is morphological microscopic analyses of the VF from autopsied patients and its correlation with basic disease and cause of death. STUDY DESIGN: Transversal cohort. MATERIAL AND METHOD: We studied 82 larynges collected during the autopsy exam and performed the Hematoxylin -eosin method for morphological analyses. RESULTS: From the 82 vestibular folds analyzed we observe that 42 (51%) showed an inflammatory reaction. In fifteen (18.3%) vestibular folds we found lymphoid follicular hyperplasia, in eleven (13.4%) diffuse inflammatory infiltrate and in sixteen (19.5%) acute inflammatory reactions. Circulatory diseases were the most frequently underlying diseases found, 31 (37.8%) and from these 20 (67.8%) presented associated vestibular folds inflammatory reaction. The infection diseases were the most frequently cause of death among the patients with inflammatory reaction of the VF. CONCLUSION: Besides the anatomic function, VF seem to have a immunological function preventing lower airway infections. Our study demonstrated inflammatory PV reactions in patients with infections diseases as cause of death; this finding could be a consequence of the sepsis that leads the patient to death or a different way used by the organism to prevent infection.

Reduction of immunity in HIV-infected individuals: can fibrosis induce hypoplasia in palatine and lingual tonsils of individuals with HIV infection?

The role of tonsils in oral immunity has been described. However, the pathogenesis of HIV infection in these organs is still unclear. The aim of this study is to perform histological and immunohistochemical analysis of the palatine and lingual tonsils of autopsied individuals with or without HIV infection. Twenty-six autopsied individuals with HIV infection (HI) (n=13) and without HIV infection (CO) (n=13) were selected. Palatine and lingual tonsil fragments were collected for histological and immunohistochemical analysis. We found in the HI group a higher frequency of hyaline degeneration in both palatine and lingual tonsils; smaller follicle areas, and a higher percentage of collagen in comparison with the CO group. In the HI group, there was higher density of blood vessels in palatine tonsils than in the CO group. In the HI group, there were significant positive correlations between palatine and lingual tonsils and the area of lymphoid follicles, and between the percentage of blood vessels and collagen in palatine tonsils. In addition, there was a significant negative correlation between the percentage of collagen and lymphoid follicle area in both palatine and lingual tonsils in the HI group. These findings suggest that the immune functions of these tonsils are prejudiced by fibrosis. Therapies to reduce the neoformation of collagen are required to improve immune function of organs against pathogens.

Colchicine attenuates left ventricular hypertrophy but preserves cardiac function of aortic-constricted rats.

To investigate the effects of colchicine on left ventricular (LV) function and hypertrophy (LVH) of rats subjected to constriction of transverse aorta (TAoC), we evaluated SO (sham operated, vehicle; n = 25), SO-T (sham operated, colchicine 0.4 mg/kg body wt ip daily; n = 38), TAoC (vehicle; n = 37), and TAoC-T (TAoC, colchicine; n = 34) on the 2nd, 6th, and 15th day after surgery. Colchicine attenuated LVH of TAoC-T compared with TAoC rats, as evaluated by ratio between LV mass (LV(M)) and right ventricular mass, LV wall thickness, and average diameter of cardiac myocytes. Systolic gradient across TAoC ( approximately 45 mmHg), LV systolic pressure, LV end-diastolic pressure, and rate of LV pressure increase (+dP/dt) were comparable in TAoC-T and TAoC rats. However, the baseline and increases of LV systolic pressure-to-LV(M) and +dP/dt-to-LV(M) ratios induced by phenylephrine infusion were greater in TAoC-T and SO-T compared with SO rats. Baseline and increases of +dP/dt-to-LV(M) ratio were reduced in TAoC compared with SO rats. TAoC rats increased polymerized fraction of tubulin compared with SO, SO-T, and TAoC-T rats. Our results indicate that colchicine treatment reduced LVH to pressure overload but preserved LV function.

Thickening of the amnion basement membrane and its relationship to placental inflammatory lesions and fetal and maternal disorders.

OBJECTIVE: The aim of this study is the morphological and morphometric analysis of the basement membrane amniotic epithelium of the chorionic plate to establish possible correlation between the basement membrane amniotic epithelium thickening and maternal and fetal disorders. STUDY DESIGN: Ninety-one placentas of infants delivered in Medical Hospital School were studied with hematoxylin-eosin (H&E) and Periodic Acid Schiff (PAS) methods, morphometric and ultrastructural analysis. RESULTS: Of the 91 placentas analyzed, 17 (18.6%) were normal with regard to placental morphology, fetal and maternal history. Basement membrane amniotic epithelium thickening was significantly greater in the cases associated with chorioamnionitis (P=0.013), villitis (P=0.040), maternal hypertension syndromes during pregnancy (P=0.027) and stillborn (P=0.040) babies. The electron microscopic examination of the basement membrane amniotic epithelium identified a structural alteration and edema of the dense lamina. CONCLUSION: Thickening of the basement membrane amniotic epithelium was associated with morphologic placental abnormalities and/or fetal or maternal disorders. Thickening of the basement membrane amniotic epithelium was identified away from the site of placental inflammation, possibly being a consequence of cytokines, supporting more than a local effect. This could be a new insight into the pathogenesis of fetal and maternal complications associated with inflammatory placental lesions.

Comparison of the total length and areas of upper central incisors between males and females using computer-assisted morphometry.

The determination of measurements of teeth facilitates various procedures in dentistry. The purpose of this study was to evaluate the total length and the area of the non-extracted upper central incisors (UCI). Periapical radiographies of 42 UCI were placed over a lighted box. The outlines of the teeth and the pulp cavity were traced onto sheets and then measured using an image analyzer. The area of the upper left central incisor tooth (tooth 21) was statistically significantly larger in males than in females (p = 0.02). The total length of the right UCI was similar to that of the left one. This study demonstrates that computer-assisted morphometry is an important tool for the evaluation of the total length and areas of teeth and their pulp cavities. The significantly larger area of tooth 21 in males compared to females has anthropomorphic and clinical implications.

Early modulation of inflammation by mesenchymal stem cell after acute kidney injury.

Therapy with stem cells has showed to be promising for acute kidney injury (AKI), although how it works is still controversial. Modulation of the inflammatory response is one possible mechanism. Most of published data relies on early time and whether the protection is still maintained after that is not known. Here, we analyzed whether immune modulation continues after 24 h of reperfusion. MSC were obtained from male Wistar rats. After 3-5 passages, cells were screened for CD73, CD90, CD44, CD45, CD29 and CD 31. In addition, MSC were submitted to differentiation in adipocyte and in osteocyte. AKI was induced by bilaterally clamping of renal pedicles for 60 min. Six hours after injury, MSC (2 x 10(5) cells) were administered intravenously. MSC-treated animals presented the lowest serum creatinine compared to non-treated animals (24 h: 1.3+/-0.21 vs. 3.23+/-0.89 mg/dl, p<0.05). The improvement in renal function was followed by a lower expression of IL-1b, IL-6 and TNF-alpha and higher expression of IL-4 and IL-10. However, 48 h after reperfusion, this cytokine profile has changed. The decrease in Th1 cytokines was less evident and IL-6 was markedly up regulated. PCNA analysis showed that regeneration occurs faster in kidney tissues of MSC-treated animals than in controls at 24 h. And also ratio of Bcl-2/Bad was higher at treated animals after 24 and 48 h. Our data demonstrated that the immunomodulatory effects of MSC occur at very early time point, changing the inflammation profile toward a Th2 profile.

Placental morphometrical and histopathology changes in the different clinical presentations of hypertensive syndromes in pregnancy.

OBJECTIVE: Even though there are clinical studies emphasizing the diagnosis and the perinatal intercurrent diseases of the Hypertensive Syndromes in Pregnancy, few of these studies establish the clinical forms of the specific hypertensive syndromes with the associated morphological placental alterations. The lack of studies on placental morphology and the etiopathogenesis of the different clinical standards for HSP, together with the need to objectively characterize these morphological placental lesions justify this study. STUDY DESIGN: A retrospective study was carried out with 91 placentas examined throughout the period from 2000 to 2003. All placentas from patients presenting HSP in this period were included in the study. These were classified according to features well established by the literature such as laboratory and clinical criteria into: gestational hypertension (GH), chronic hypertension (CH), pre-eclampsia (PE) and pre-eclampsia superimposed on chronic hypertension (PSCH). RESULTS: The number of knots presented a positive correlation with the length of time and severity of the hypertension during gestation (Spearman correlation: 0.253; P = 0.0158). The fibrin deposit was greater in all HSP groups but the pattern of distribution changes in the most severe cases from perivillous to intravillous as in the PSCH group (P = 0.002). There was no statistically significant difference in the area of the stem vessel walls among the groups. The cases with PE and CH presented a larger number of terminal villi vessels (P < 0.001). CONCLUSION: This report suggests, that although they could be different types of hypertension or an evaluation of the same disease, the final pathway that leads to microscopic lesions in the placenta is the same, with only different intensity due to the severity of the disease.

Expression of PDX-1 is reduced in pancreatic islets from pups of rat dams fed a low protein diet during gestation and lactation.

Intrauterine and early postnatal malnutrition has profound consequences on fetal and postnatal development in both humans and animals. In addition, low birth weight has been reported to be associated with impaired insulin secretion, insulin resistance and diminished area of pancreatic islets. Because the transcription factor pancreatic and duodenal homeobox 1 (PDX-1) is important for the maintenance of B-cell physiology, PDX-1 expression and islet area were assessed in neonatal rats of dams fed low (6%) or normal (17%) protein diets during pregnancy. PDX-1 protein and mRNA levels, as well as insulin secretion and islet area, were measured after 28 d of life in normal, low protein and recovered rats whose dams consumed a normal protein diet after delivery. Insulin secretion by isolated islets in response to 2.8 and 16.7 mmol glucose/L was reduced in 28-d-old low protein rats compared with the control (P < 0.05). At birth and after 28 d of life, the islet area and PDX-1 protein expression were also reduced (P < 0.05). In contrast, PDX-1 mRNA levels in islets from 28-d-old low protein rats were not different from control rats. PDX-1 protein expression in pancreatic islets, the area of islets and insulin secretion were restored in recovered rats, whereas PDX-1 mRNA levels were higher than in normal rats (P < 0.05). These results suggest a link among diminished PDX-1 protein expression, a reduction in islet area and impaired insulin secretion in low protein rats. The reintroduction of a normal diet early in life restored islet area and cell physiology.

Descricão das lesões microscópicas das pregas vestibulares de adultos autopsiados e sua relacão com as causas de óbito e doenca de base / Description of microscopic lesions of vestibular folds of autopsied adults and their relationship with cause of death and underlying disease

Com o aumento dos métodos invasivos que são utilizados para o diagnóstico de doencas do trato respiratório é de se esperar que as alteracões das pregas vestibulares (PV) sejam mais freqüentes. Além disso, recentemente tem sido discutida a importância das PV na protecão do organismo contra agentes infecciosos e pouco se sabe sobre as lesões microscópicas em pacientes autopsiados, pois o estudo das cordas vocais não é rotina no exame post mortem. OBJETIVO: O objetivo deste estudo foi descrever as alteracões microscópicas das pregas vestibulares e realizar a sua relacão com as causas de óbito e doenca de base de adultos autopsiados. FORMA DE ESTUDO: coorte transversal. MATERIAIS E MÉTODOS: Foram estudadas microscopicamente 82 laringes coletadas de adultos autopsiados sendo realizada a coloracão da Hematoxilina-eosina para visualizar as alteracões morfológicas microscópicas das PV. RESULTADOS: Das 82 PV analisadas, observamos que 42 (51 por cento) apresentaram reacão inflamatória, sendo esta a única lesão encontrada. Quinze (18,3 por cento) casos apresentaram hiperplasia dos folículos linfóides, onze (13,4 por cento) casos infiltrado inflamatório difuso intenso e 16 (19,5 por cento), reacão inflamatória aguda. As doencas de base mais freqüentemente encontradas foram as do grupo de doencas do aparelho circulatório 31 (37,8 por cento) e nestas 20 (67,8 por cento) apresentavam reacão inflamatória das PV. As doencas infecciosas foram a causa de morte mais freqüente nos pacientes com reacão inflamatória das pregas vestibulares. CONCLUSAO: Além da funcão anatômica as PV parecem possuir uma funcão imunológica em relacão à infecccão das vias aéreas inferiores. Nosso estudo demonstrou a presenca de reacão inflamatória nas cordas vocais em pacientes com doencas infecciosas como causa de morte, podendo este achado estar relacionado com o processo séptico generalizado que levou o indivíduo à morte ou ser uma das formas do organismo prevenir a penetracão de agentes infecciosos.

Ocorrência de cisticercose (Cysticercus cellulosae) encefálica e cardíaca em necropsias / Occurrence of encephalic and cardiac cysticercosis (Cysticercus cellulosae) in necropsy

Objetivo: Realizar estudo retrospectivo ao achado de lesöes de cisticercose e às localizaçöes mais comumente atingidas em exames usuais de necropsias. Métodos: Foram revistos, retrospectivamente, 1.596 protocolos de necropsias em Uberaba, MG, Brasil, no período de 1974 a 1997, registrando-se: a idade, o sexo, a cor, o índice de massa corporal (IMC) e a localizaçäo do cisticerco. Resultados: Encontraram-se relatos de cisticercose em 53 (3,3 por cento) protocolos. A média das idades foi de 50 + ou - 15,4 anos (variando de 15 a 86 anos), 62,3 por cento eram homens, 64,1 por cento brancos. As localizaçöes encontradas foram: encefálica (79,2 por cento), cardíaca (22,6 por cento), muscular esquelética (11,3 por cento) e outras (5,7 por cento). Näo houve diferença estatística das variáveis entre os grupos positivos ou negativos para o diagnóstico de cisticercose. Observaram-se dois casos de neurocisticercose localizados no núcleo ventromedial do hipotálamo. Conclusäo: A ocorrência de cisticercose, bem como a localizaçäo cardíaca foram mais freqüentemente encontradas em relaçäo a outros estudos da regiäo. Em dois casos de cisticercose hipotalâmica havia associaçäo com obesidade

Budd-chiari syndrome and unsuspected gastric adenocarcinoma

The Budd-Chiari syndrome has not been described in young patients with gastric cancer. A case of Budd-Chiari syndrome and carcinomatous Iymphangitis is reported in a 28 years-old white man with unsuspected gastric cancer, presenting jaundice, hematemesis and dyspnea. Autopsy disciosed gastric adenocarcinoma invading vessels of the submucous and serous layers, with gastric and intestinal bleeding, liver and lung metastases. Multiple mixed (fibrin, platelets and tumor cells) microthrombi were observed in small pulmonary blood vessels, and both subpleural Iymph vessels and lung interstitium contained metastatic tumor cells.