1,721,022 research outputs found

    Fetal programming of neuropsychiatric disorders

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    Starting from the Developmental Origins of Health and Disease (DOHaD) hypotheses proposed by David Barker, namely fetal programming, in the past years, there is a growing evidence of the major role played by epigenetic factors during the intrauterine life and the perinatal period. Furthermore, it has been assessed that these factors can affect the health status in infancy and even in adulthood. In this review, we focus our attention on the fetal programming of the brain, analyzing the most recent literature concerning the epigenetic factors that can influence the development of neuropsychiatric disorders such as bipolar disorders, major depressive disorders, and schizophrenia. The perinatal epigenetic factors have been divided in two main groups: maternal factors and fetal factors. The maternal factors include diet, smoking, alcoholism, hypertension, malnutrition, trace elements, stress, diabetes, substance abuse, and exposure to environmental toxicants, while the fetal factors include hypoxia/asphyxia, placental insufficiency, prematurity, low birth weight, drugs administered to the mother or to the baby, and all factors causing intrauterine growth restriction. A better comprehension of the possible mechanisms underlying the pathogenesis of these diseases may help researchers and clinicians develop new diagnostic tools and treatments to offer these patients a tailored medical treatment strategy to improve their quality of life

    Parotid tumours: clinical and oncologic outcomes after microscope-assisted parotidectomy with intraoperative nerve monitoring

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    I pazienti sottoposti ad intervento chirurgico di parotidectomia per lesioni benigne e maligne possono presentare disfunzioni temporanee o permanenti del nervo facciale. Il monitoraggio intraoperatorio della motilità facciale è uno strumento ampiamente riconosciuto per la sua utilità nella preservazione del nervo, mentre l’efficacia del microscopio operatorio è stata raramente discussa. Gli autori riportano la loro esperienza su 198 parotidectomie consecutive eseguite su 196 pazienti con l’ausilio del microscopio operatorio e del monitoraggio intraoperatorio del nervo facciale. Centoqurantacinque interventi sono stati eseguiti per lesioni benigne e 53 per neoplasie maligne. Tredici pazienti operati per lesioni benigne hanno presentato un deficit della funzionalità del nervo facciale: 11 hanno sofferto di paralisi temporanea e 2 di paralisi permanente (entrambe di secondo grado). Dieci pazienti affetti da patologia maligna presentavano un interessamento preoperatorio del nervo facciale. Cinque e 6 pazienti affetti da patologia maligna senza interessamento preoperatorio del nervo hanno presentato un deficit rispettivamente temporaneo e definitivo (in 2 casi il sacrificio di un ramo del nervo macroscopicamente infiltrato dalla neoplasia fu deciso solo durante la procedura chirurgica). L’incidenza di paralisi definitiva di una singola branca del nervo facciale dopo interventi eseguiti per lesioni che non originavano dal nervo facciale o che non lo infiltravano macroscopicamente (n = 185) è stata del 2,7%. I pazienti trattati per tumori benigni non flogistici del lobo superficiale della ghiandola parotide (n = 91) hanno presentato una paralisi facciale postoperatoria temporanea nel 4,4% dei casi e nessun deficit permanente. L’uso combinato del microscopio operatorio e del monitoraggio intraoperatorio del nervo sembra garantire la preservazione del nervo facciale nei pazienti sottoposti a parotidectomia.Temporary and permanent facial nerve dysfunctions can be observed after parotidectomy for benign and malignant lesions. Intraoperative nerve monitoring is a recognised tool for the preservation of the nerve, while the efficacy of the operative microscope has been rarely stated. The authors report their experience on 198 consecutive parotidectomies performed on 196 patients with the aid of the operative microscope and intraoperative nerve monitoring. 145 parotidectomies were performed for benign lesions and 53 for malignancies. Thirteen patients treated for benign tumours experienced temporary (11 cases) or permanent facial palsy (2 cases, both of House-Brackmann grade II). Ten patients with malignant tumour presented with preoperative facial nerve weakness that did not improve after treatment. Five and 6 patients with malignant lesion without preoperative facial nerve deficit experienced postoperative temporary and permanent weakness respectively (the sacrifice of a branch of the nerve was decided intraoperatively in 2 cases). Long-term facial nerve weakness after parotidectomy for lesions not directly involving or originating from the facial nerve (n = 185) was 2.7%. Patients treated for benign tumours of the extra facial portion of the gland without inflammatory behaviour (n = 91) had 4.4% facial nerve temporary weakness rate and no permanent palsy. The combined use of the operative microscope and intraoperative nerve monitoring seems to guarantee facial nerve preservation during parotidectomy

    Morphogenesis and molecular mechanisms involved in human kidney development

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    The development of the human kidney is a complex process that requires interactions between epithelial and mesenchymal cells, eventually leading to the coordinated growth and differentiation of multiple highly specialized stromal, vascular, and epithelial cell types. The application of molecular biology and immunocytochemistry to the study of cell types involved in renal morphogenesis is leading to a better understanding of nephrogenesis, which requires a fine balance of many factors that can be disturbed by various prenatal events in humans. The aim of this paper is to review human kidney organogenesis, with particular emphasis on the sequence of morphological events, on the immunohistochemical peculiarities of nephron progenitor populations and on the molecular pathways regulating the process of mesenchymal to epithelial transition. Kidney development can be subdivided into five steps: (i) the primary ureteric bud (UB); (ii) the cap mesenchyme; (iii) the mesenchymalepithelial transition; (iv) glomerulogenesis and tubulogenesis; (v) the interstitial cells. Complex correlations between morphological and molecular events from the origin of the UB and its branching to the metanephric mesenchyme, ending with the maturation of nephrons, have been reported in different animals, including mammals. Marked differences, observed among different species in the origin and the duration of nephrogenesis, suggest that morphological and molecular events may be different in different animal species and mammals. Further studies must be carried out in humans to verify at the morphological, immunohistochemical, and molecular levels if the outcome in humans parallels that previously described in other specie

    Immunohistochemical markers of stem/progenitor cells in the developing human kidney

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    The aim of this study was to better define, by immunohistochemistry, the molecular markers of renal stem/progenitor cells localized in the different niches of ten human preterm kidneys with gestational age ranging from 11 up to 25 weeks. Our data evidence the existence of multiple stem/progenitor pools in different zones of the human developing kidney that are characterized by different phenotypes: capsular stem cells were EMA (MUC1)+, MDM2+, Vimentin+ and Wnt1+; progenitors of the sub-capsular nephrogenic zone were MDM2+ and Wnt1+; cap mesenchymal cells were EMA (MUC1)+, CD15+, vimentin+, Wt1+, CD10+, Bcl2+, Wnt1+ and PAX2+; interstitial progenitor cells were Vimentin+, Wt1+ and α1Anti-tripsin+. Our data evidence the existence of multiple stem/progenitor cell pools in the fetal and neonatal human kidney. Progenitors of these different pools are characterized by a peculiar phenotype, indicating a different differentiation stage of these renal progenitors. A better knowledge of the molecular markers expressed by renal stem/progenitors might represent a relevant datum for researchers involved in renal regenerative medicine

    From ureteric bud to the first glomeruli: genes, mediators, kidney alterations

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    The development of the mammalian kidney is a complex and in part unknown process which requires interactions between pluripotential/stem cells, undifferentiated mesenchymal cells, epithelial and mesenchymal components, eventually leading to the coordinate development of multiple different specialized epithelial, endothelial and stromal cell types within the kidney architectural complexity. We will describe the embryology and molecular nephrogenetic mechanisms, a fascinating traffic of cells and tissues which takes place in five stages: (1) ureteric bud (UB) development; (2) cap mesenchyme formation; (3) mesenchymal–epithelial transition (MET); (4) glomerulogenesis and tubulogenesis; (5) interstitial cell development. In particular, we will analyze the multiple cell types involved in these dramatic events as characters moving between different worlds, from the mesenchymal to the epithelial world and back, and will start to define the multiple factors that propel these cells during their travels throughout the developing kidney. Moreover, according with the hypothesis of renal perinatal programing, we will present the results reached in the fields of immunohistochemistry and molecular biology, by means of which we can explain how a loss or excess of molecular factors governing nephrogenesis may cause the onset of pathologies of different gravity, in some cases leading to a chronic kidney disease at different times from birth
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