Expression of vascular endothelial growth factor (VEGF) and factor VIII in the gilt placenta and its relation to fetal development.

Vascular endothelial growth factor (VEGF) and von Willebrand factor (Factor VIII) are important components involved in the regulation of vascular development and identification of endothelial cells in many tissues. This study aimed to evaluate the presence of these substances in the placenta of pig fetuses located in different uterine regions and at different gestational ages and correlate them with fetal development. One hundred seventy-five pig fetuses from fifteen gilts slaughtered at 50, 80 and 106 days of pregnancy were used. Each uterine horn was divided into three segments, the apex, base and middle region, and also into left and right sides. The fetuses were sexed before determining their weight and anatomical measurements. The weights of the placentas were obtained for the calculation of placental efficiency, and VEGF and factor VIII were determined by immunohistochemistry. There was no significant interaction between gestational age, uterine segment or side and fetal sex in any of the variables studied. Higher VEGF and factor VIII concentrations were found at 80 and 105 days of pregnancy, and there was no significant difference between the right and left sides of the uterus, uterine segments or fetal sex. Positive correlations between VEGF and fetal weights were observed at 80 and 105 days of pregnancy, whereas factor VIII showed positive correlations with the weight and length of fetuses and placental weight and efficiency throughout pregnancy. It was concluded that VEGF and factor VIII are important growth factors associated with fetal development in pigs and are identified in all uterine segments. The concentration of these substances increases until the middle third of pregnancy which suggests that most of the uterine vascular development occurs before this stage.

Effects of transcutaneous electrical nerve stimulation on fetal and placental development in an experimental model of placental insufficiency.

OBJECTIVE: To elucidate the effects of transcutaneous electrical nerve stimulation (TENS) in pregnancies with placental insufficiency. METHODS: Pregnant rats were subjected to uterine artery ligation and to TENS according to the following groups: ligated stimulated (LS); ligated non-stimulated (LN), control stimulated (CS); and control non-stimulated (CN). Fetal external measurements, such as crown-rump length (CRL), fronto-occipital distance (FOD), thoracic ventral-dorsal (TVDD) and abdominal ventral-dorsal (AVDD) distances were analyzed together with the area occupied by fetal internal organs. Glucose transporter 1 (GLUT-1) expression was evaluated by immunohistochemistry in fetal organs. Thickness of junctional, labyrinth and intermediate placental zones was analyzed by morphometric evaluation in HE-stained slides, and placental hypoxia-inducible factor 1 alfa expression was measured by real-time polymerase chain reaction. RESULTS: In LN and CS groups compared to the CN group, CRL was reduced (27.51/28.95 versus 30.16 mm), as well as FOD (6.63/6.63 versus 7.36 mm), AVDD (7.38/8.00 versus 8.61 mm) and TVDD (6.46/6.87 versus 7.23 mm). Brain GLUT-1 expression was higher in LS (1.3%) and CS (1.8%). The area occupied by placental vessels in the labyrinth zone (29.67 ± 3.51 versus 20.83 ± 7.63) and intermediate zone (26.46 ± 10.21 versus 10.86 ± 8.94) was larger in the LS group than in the LN group. CONCLUSIONS: Our results suggest a negative effect of TENS on placental development, thus compromising the maintenance of adequate blood flow to the fetus.

Acute kidney injury and progression of renal failure after fetal programming in the offspring of diabetic rats.

BACKGROUND: Diseases of adulthood, such as diabetes and hypertension, may be related to changes during pregnancy, particularly in kidney. We hypothesized that acute kidney injury progresses more rapidly in cases of fetal programming. METHODS: Diabetic dams' offspring were divided into: CC (controls, receiving vehicle); DC (diabetics, receiving vehicle); CA (controls receiving folic Acid solution, 250 mg/kg); and DA (diabetics receiving folic acid solution). Renal function tests, morphometry, gene, and protein expression of epithelial-mesenchymal transition (EMT) markers were analyzed by qPCR and immunohistochemistry, respectively. RESULTS: Creatinine, urea, Bowman's space, and EMT markers were increased in CA and DA groups. TGF-ß3, actin, and fibronectin expression was higher in CA and DA, with significant increase in DA compared to CA 2-mo offspring. There was higher expression level of TGF-ß1, TGF-ß3, fibronectin, and vimentin in the offspring of diabetic dams at 5 mo. Increases in TGF-ß1 and TGF-ß3 were more evident in the offspring of diabetic dams. CONCLUSION: Fetal programming promotes remarkable changes in kidney morphology, and function in offspring and renal failure progression may be faster in younger offspring of diabetic dams subjected to an additional injury.

Interleukin-6 and C-reactive protein are overexpressed in the liver of perinatal deaths diagnosed with fetal inflammatory response syndrome.

Anatomopathologic studies have failed to define the fetal inflammatory response syndrome (FIRS) as a cause of fetal death. Here, liver fragments of perinatal autopsies were collected at a university hospital from 1990 to 2009 and classified according to the cause of death, perinatal stress, and gestational age (GA) of the fetus. IL-6, TNF-α, and C-reactive protein (CRP) expression were immunostained, respectively, with primary antibody. Cases with congenital malformation, ascending infection, and perinatal anoxia showed increased IL-6, CRP, and TNF-α, respectively. Prematures presented higher expression of IL-6 whereas term births showed higher expression of CRP. Cases classified as acute stress presented higher expression of IL-6 and TNF-α and cases with chronic stress presented higher expression of CRP. GA correlated negatively with IL-6 and positively with CRP and TNF-α. Body weight correlated negatively with IL-6 and positively with CRP and TNF-α. Despite the diagnosis of FIRS being clinical and based on serum parameters, the findings in the current study allow the inference of FIRS diagnosis in the autopsied infants, based on an in situ liver analysis of these markers.

CD28 family and chronic rejection: "to belatacept...And beyond!".

Kidneys are one of the most frequently transplanted human organs. Immunosuppressive agents may prevent or reverse most acute rejection episodes; however, the graft may still succumb to chronic rejection. The immunological response involved in the chronic rejection process depends on both innate and adaptive immune response. T lymphocytes have a pivotal role in chronic rejection in adaptive immune response. Meanwhile, we aim to present a general overview on the state-of-the-art knowledge of the strategies used for manipulating the lymphocyte activation mechanisms involved in allografts, with emphasis on T-lymphocyte costimulatory and coinhibitory molecules of the B7-CD28 superfamily. A deeper understanding of the structure and function of these molecules improves both the knowledge of the immune system itself and their potential action as rejection inducers or tolerance promoters. In this context, the central role played by CD28 family, especially the relationship between CD28 and CTLA-4, becomes an interesting target for the development of immune-based therapies aiming to increase the survival rate of allografts and to decrease autoimmune phenomena. Good results obtained by the recent development of abatacept and belatacept with potential clinical use aroused better expectations concerning the outcome of transplanted patients.

Collagenofibrotic glomerulopathy: three case reports in Brazil.

BACKGROUND: We are reporting the first collagenofibrotic glomerulopathy (CG) in South America. So, this collagen type III glomerulopathy is not limited to Japan but may be found throughout the world. CASE REPORTS: We describe three patients that presented some factors in common, such as sex, age and the presence of non-nephrotic proteinuria associated with microscopic hematuria. The findings with the immunofluorescence microscopy, of immunoglobulins, and components of the complement were usually negative. The picrosyrius staining showed the presence of reddish material in the mesangium, when it was seen under standard microscopy; however, when it was seen with birefringence, it became greenish under polarized light, showed the collagen found in this area of the glomerulus. The identification of CG was made through electronic microscopic scanning, and curved and disorganized fibers were found. CONCLUSION: These cases are the first from South America to be reported, and they are about an idiopathic renal disease that is not related to any specific races or locations. The reports contribute to a better understanding of this disease, which although not so prevalent, should be considered as an importantly differential diagnostic of cases of proteinuria.

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.

Cushing's disease in a 5-month infant due to a basophilic microadenoma of the pituitary gland.

We report a female patient who developed severe Cushing's disease during the fifth month of life due to a basophilic pituitary adenoma Histological findings showed a basophilic microadenoma of the pituitary gland, leading to the diagnosis of Cushing's disease. The infant died because of untreatable septic shock. The importance of the present report resides in the age of the child at diagnosis, and that it was the necropsy finding of microadenoma which clarified the cause of the Cushing's syndrome, since it was not diagnosed during life. Cushing's disease is most often diagnosed in children older than 7 years, and our patient was only 5 months old when we detected the pituitary adenoma, the earliest case diagnosed so far. Cushing's syndrome in pediatric patients has been rarely reported and most cases are due to functioning adrenal tumors, usually a malignant carcinoma but occasionally a benign adenoma. The present case shows that the pituitary of these patients should be investigated with important implications in terms of therapeutic approaches, such as pituitary radiotherapy, which can cure the patient when treatment is started very soon.

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.

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.