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1.
J Proteome Res ; 19(1): 300-313, 2020 Jan 03.
Artigo em Inglês | MEDLINE | ID: mdl-31638822

RESUMO

Because of the distinctive features of the oral cavity, the determination of the proteins involved in the formation of the "oral protein pellicle" is demanding. The present study investigated the susceptibility of several human basic proline-rich peptides, named P-H, P-D, P-F, P-J, and II-2, as substrates of transglutaminase-2. The reactivity of the P-C peptide and statherin was also investigated. Peptides purified from human whole saliva were incubated with the enzyme in the presence or in the absence of monodansyl-cadaverine. Mass spectrometry analyses of the reaction products highlighted that P-H and P-D (P32 and A32 variants) were active substrates, II-2 was less reactive, and P-F and P-J showed very low reactivity. P-C and statherin were highly reactive. All of the peptides formed cyclo derivatives, and only specific glutamine residues were involved in the cycle formation and reacted with monodansyl-cadaverine: Q29 of P-H, Q37 of P-D, Q21 of II-2, Q41 of P-C, and Q37 of statherin were the principal reactive residues. One or two secondary glutamine residues of only P-H, P-D P32, P-C, and statherin were hierarchically susceptible to the reaction with monodansyl-cadaverine. MS and MS/MS data were deposited to the ProteomeXchange Consortium ( http://www.ebi.ac.uk/pride ) via the PRIDE partner repository with the data set identifier PXD014658.

2.
J Neuroradiol ; 47(3): 203-209, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-30439395

RESUMO

PURPOSE: To explore the association between presence of inflammatory cells in the carotid plaques surgically treated and brain MRI findings. MATERIAL AND METHODS: Forty consecutive patients were prospectively analyzed. Brain MRI was performed with a 1.5 Tesla scanner and infacts (lacuna and non-lacunar) pertinence of the anterior circulation were recorded. All patients underwent carotid endarterectomy "en bloc"; carotid plaques histological sections were prepared and immuno-cytochemical analysis was performed to characterize and quantify the presence of inflammatory cells. ROC curve analysis, Pearson Rho correlation and Mann-Whitney test were applied. RESULTS: The immuno-cytochemical analysis demonstrated that plaques of symptomatic patients (stroke\TIA; n = 25) had more inflammatory cells, mainly macrophages (CD68) compared with plaques of patients without symptoms (Mann-Whitney = P < 0.001, ROC curve area = 0.901). Correlation analysis showed a statistically significant association between the number of brain non-lacunar infarcts and the entity of macrophages (P < 0.001); whereas no association with lacunar infarcts (P = 0.1934) was found. CONCLUSION: Results of this preliminary study suggest that the presence and amount of inflammatory cells within carotid artery plaque is associated with cerebrovascular events and with the number of MRI brain detectable infarct.

3.
Ann Med Surg (Lond) ; 46: 17-22, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31485327

RESUMO

Background: The incidence of node metastases in papillary thyroid carcinoma (PTC) is high, ranging from 20% to 90%. Prophylactic central lymph node compartment dissection (CLND), suggested from the latest guidelines for high-risk tumors, meets resistance due to the high incidence of postoperative complications. Recently, new molecular biologic techniques, such as One Step Nucleic Acid Amplification (OSNA), have spread widely, allowing to quickly isolate, amplify and quantify mRNA encoding for proteins selectively present in neoplastic cells, as Cytokeratine-19. The aim of this study is to evaluate the application of OSNA to intraoperative diagnosis of node metastases of PTC. Methods: We included in the study patients with preoperative diagnosis of PTC; from each patient one or more lymph nodes were collected. To assess OSNA accuracy, each lymph node was divided into two halves: the first one was analysed with histopathological and immunohistochemical examination, whereas the second was studied with OSNA. Results: Twenty-six lymph nodes from 13 patients were included in the study. Overall, OSNA sensitivity was 87.5%, specificity 94.4%, positive predictive value 87.5%, negative predictive value 94.4% and accuracy 92.8%. Discussion and conclusion: OSNA is effective in detecting lymph node metastases of PTC. Considering the high risk of complications in CLND, and the uncertain prognostic value of lymph node metastases of PTC, OSNA seems to be a promising tool to identify intraoperatively patients who may benefit from CLND.

4.
Am J Perinatol ; 36(S 02): S33-S36, 2019 07.
Artigo em Inglês | MEDLINE | ID: mdl-31238356

RESUMO

In the present article, we discuss the following topics: (1) the fetal programming of adult kidney diseases and (2) the role of neonatologists in the regenerative renal medicine, based on the activation of resident renal SC. Here, we report the most important steps of our collaboration between neonatologists, nephrologists, and pathologists. Nephrologists should be more interested in clinical data regarding the first month of life in the womb of their adult patients, being particularly focused on birth weight and on the weeks of gestation at birth, without forgetting data regarding maternal status during gestation and neonatal asphyxia. Neonatologists should be aware that any preterm or low birthweight infant should be considered as a subject with fewer glomeruli, probably predicted to develop renal disease later in life.


Assuntos
Nefropatias/etiologia , Rim/embriologia , Epigênese Genética , Humanos , Recém-Nascido de Baixo Peso , Recém-Nascido , Recém-Nascido Prematuro , Nefropatias/genética , Nefropatias/prevenção & controle , Neonatologia , Néfrons/embriologia , Papel do Médico
5.
Gynecol Oncol ; 154(1): 60-64, 2019 07.
Artigo em Inglês | MEDLINE | ID: mdl-31126637

RESUMO

OBJECTIVE: This study aimed to determine the prevalence of occult pelvic lymph node metastasis in patients with endometrial cancer (EC) with isolated paraaortic dissemination who underwent pelvic and paraaortic lymphadenectomy. METHODS: From 2004 to 2008, patients undergoing surgery for EC at our institution were prospectively treated according to a validated surgical algorithm relying on intraoperative frozen section. For the current study, we re-reviewed pathologic slides obtained at the time of diagnosis and performed ultrastaging of all negative pelvic lymph nodes to assess the prevalence of occult pelvic lymph node metastasis. RESULTS: Of 466 patients at risk for lymphatic dissemination, 394 (84.5%) underwent both pelvic and paraaortic lymphadenectomy. Of them, 10 (2.5%) had isolated paraaortic metastasis. Pathologic review of hematoxylin-eosin-stained slides identified 1 patient with micrometastasis in 1 of 18 pelvic lymph nodes removed. Ultrastaging of 296 pelvic lymph nodes removed from the 9 other patients (median [range], 32 [20-50] nodes per patient) identified 2 additional cases (1 with micrometastasis and 1 with isolated tumor cells), for a total of 3/10 patients (30%) having occult pelvic dissemination. CONCLUSIONS: Ultrastaging and pathologic review of negative pelvic lymph nodes of patients with presumed isolated paraaortic metastasis can identify occult pelvic dissemination and reduce the prevalence of true isolated paraaortic disease. In the era of the sentinel lymph node (SLN) algorithm for EC staging, which incorporates ultrastaging of the SLNs removed, these findings demonstrate that use of the SLN algorithm can further mitigate the concern of missing cases of isolated paraaortic dissemination.


Assuntos
Neoplasias do Endométrio/patologia , Linfonodos/patologia , Idoso , Aorta , Neoplasias do Endométrio/epidemiologia , Neoplasias do Endométrio/cirurgia , Feminino , Humanos , Itália/epidemiologia , Excisão de Linfonodo , Linfonodos/cirurgia , Metástase Linfática , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Prevalência
6.
Am J Dermatopathol ; 41(6): 453-455, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-30461425

RESUMO

Nevus comedonicus is a rare cutaneous follicular hamartoma, characterized by the clustering of papules with firm, blackened horny buffers. It is usually present at birth or during childhood, although few cases of late-onset disease have been described. We present a case of postmenopausal-onset nevus comedonicus in a 55-year-old white woman without relevant medical history. Skin biopsy showed the typical features of several cyst-dilated follicular structures occupied by keratotic material and the peculiar finding of epidermolytic hyperkeratosis of the follicular epithelial walls. A brief review of the clinical and histological features of other similar cases published in the literature is performed.


Assuntos
Hamartoma/patologia , Hiperceratose Epidermolítica/patologia , Dermatopatias/patologia , Feminino , Humanos , Pessoa de Meia-Idade
8.
Expert Rev Mol Diagn ; 18(6): 499-512, 2018 06.
Artigo em Inglês | MEDLINE | ID: mdl-29708446

RESUMO

INTRODUCTION: BRAF mutant colorectal cancer (BRAF MT CRC) is a unique category of colorectal tumour with peculiar molecular, pathological and clinical features and poor prognosis; despite recent research, BRAF mutation predictive value and standard treatment of BRAF MT CRC still have to be defined. In this review, we focused on this challenging topic. Areas covered: The potential use of BRAF mutational status among recent additional prognostic and predictive indicators and current treatment strategy in use in these patients is discussed. Moreover, implications and characteristics of new BRAF mutations other than BRAFV600E are analyzed. An in-deep outlook on the immediate future for clinical and translational research in this subgroup of patients is also presented, such as combination therapy with agents targeting the RAS/RAF/MEK/ERK pathway and standard chemotherapy in order to overcome resistance. We performed a research on Pubmed typing 'BRAF mutation', 'colorectal cancer', 'predictive and prognostic value', 'targeted therapy', 'BRAF inhibition'. Expert commentary: BRAFV600E mutation represents a strong, independent negative prognostic factor in II-III stage MSS CRC and mCRC. The best treatment still has to be identified; currently, in good performance status patients, an intensive-chemotherapy-combination remains the standard of care. Further investigations are warranted to explore new horizons to change BRAF MT mCRC outcomes.


Assuntos
Neoplasias Colorretais , Sistema de Sinalização das MAP Quinases , Glicoproteínas de Membrana , Mutação de Sentido Incorreto , Sulfotransferases , Substituição de Aminoácidos , Animais , Neoplasias Colorretais/diagnóstico , Neoplasias Colorretais/tratamento farmacológico , Neoplasias Colorretais/genética , Neoplasias Colorretais/metabolismo , Humanos , Sistema de Sinalização das MAP Quinases/efeitos dos fármacos , Sistema de Sinalização das MAP Quinases/genética , Glicoproteínas de Membrana/antagonistas & inibidores , Glicoproteínas de Membrana/genética , Glicoproteínas de Membrana/metabolismo , Prognóstico , Sulfotransferases/antagonistas & inibidores , Sulfotransferases/genética , Sulfotransferases/metabolismo
9.
Orphanet J Rare Dis ; 13(1): 79, 2018 05 16.
Artigo em Inglês | MEDLINE | ID: mdl-29769092

RESUMO

BACKGROUND: Alpha-1-antitrypsin (AAT) deficiency (AATD) of Z, Mmalton, Siiyama type is associated with liver storage of the mutant proteins and liver disease. The Z variant can be diagnosed on isoelectric focusing (IEF) while Mmalton and Siiyama may be missed or misdiagnosed with this technique. Therefore, molecular analysis is mandatory for their characterization. In particular, that holds true for the Mmalton variant as on IEF profile it resembles the wild M2 subtype. METHODS: This is a retrospective analysis involving review of medical records and of liver biopsy specimens from a series of Mmalton, Z and Siiyama Alpha-1-antitrypsin deficiency patients. The review has been implemented by additional histological stains, electron microscopic observations and 3-D modeling studies of the sites of the mutations. RESULTS: Z, Mmalton and Siiyama liver specimen contained characteristic intrahepatocytic PAS-D globules. The globules differed in the three variants as only Mmalton cases showed dark basophilic precipitates within the AAT inclusions. The precipitates were visualized in haematoxylin-eosin (H.E.) stained preparations and corresponded to calcium precipitates as demonstrated by von Kossa staining. On immunohistochemistry, ZAAT inclusions were stained by polyclonal as well as monoclonal noncommercial anti-AAT antibody (AZT11), whilst Mmalton and Siiyama inclusion bodies remained negative with the monoclonal anti-Z antibody. 3-D protein analysis allowed to predict more severe misfolding of the Mmalton molecule as compared to Z and Siiyama that could trigger anomalous interaction with endoplasmic reticulum chaperon proteins, namely calcium binding proteins. CONCLUSIONS: Mmalton AAT inclusion bodies contain calcium precipitates inside them that allow the differential diagnosis with Siiyama and ZAAT inclusions in routine histological sections. The study has confirmed the specificity of the monoclonal AZT11 for the Z mutant. Thus, the combination of these two features is crucial for the distinction between the three variants and for predicting the genotype, whose confirmation would definitely require molecular analysis. Our study provides new data on the pathomorphogenesis of Mmalton inclusion bodies whose mineralization could play a central role in disease pathogenesis of Mmalton that is distinct from the Z and Siiyama variants. Calcium is known to be a major effector of cell death either via the increased intracellular concentration or the alteration of homeostasis.


Assuntos
Corpos de Inclusão/metabolismo , Deficiência de alfa 1-Antitripsina/metabolismo , alfa 1-Antitripsina/metabolismo , Animais , Cálcio/metabolismo , Genótipo , Humanos , Fígado/metabolismo , Fígado/patologia , Registros Médicos , Mutação/genética , Estudos Retrospectivos , alfa 1-Antitripsina/genética , Deficiência de alfa 1-Antitripsina/genética
10.
Neurosci Lett ; 669: 75-82, 2018 03 16.
Artigo em Inglês | MEDLINE | ID: mdl-27818357

RESUMO

The study of neuropathological markers in patients affected by mental/psychiatric disorders is relevant for the comprehension of the pathogenesis and the correlation with the clinical symptomatology. The neuropathology of Alzheimer's disease (AD) recognizes intraneuronal and extracellular neurofibrillary formation responsible for neuronal degeneration. Immunohistochemical studies discovered many interesting results for a better interpretation of the AD pathogenesis, while the "metal hypothesis" supports that metal ions might differentially influence the formation of amyloid aggregates. The most relevant pathological findings reported in schizophrenia originate from computer assisted tomography (CT), Magnetic Resonance Imaging (MRI) studies and Diffusion Tensor Imaging (DTI), suggesting the brain abnormalities involved in the pathophysiology of schizophrenia. The theory of fetal programming illustrates the epigenetic factors that may act during the intrauterine life on brain development, with relevant consequences on the susceptibility to develop AD or schizophrenia later in life. The neuropathological interpretation of AD and schizophrenia shows that the presence of severe neuropathological changes is not always associated with severe cognitive impairment. A better dialogue between psychiatrics and pathologists might help to halt insurgence and progression of neurodegenerative diseases.


Assuntos
Doença de Alzheimer/patologia , Desenvolvimento Fetal , Esquizofrenia/patologia , Doença de Alzheimer/genética , Doença de Alzheimer/metabolismo , Biomarcadores , Encéfalo/metabolismo , Encéfalo/patologia , Epigênese Genética , Humanos , Sobrecarga de Ferro/metabolismo , Sobrecarga de Ferro/patologia , Esquizofrenia/genética , Esquizofrenia/metabolismo
11.
Curr Med Chem ; 25(1): 75-84, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-28359231

RESUMO

BACKGROUND: Research into gold-based drugs for a range of human diseases has seen a revival in recent years. This article reviews the most important applications of gold products in different fields of human pathology. Au(I) and Au(III) compounds have been re-introduced in clinical practice for targeting the cellular components involved in the onset and progression of viral and parasitic diseases, rheumatoid arthritis and cancer. RESULTS: After some brief historical notes, this article takes into account the applications of gold compounds against Mycobacterium tuberculosis, and also in tuberculosis and in rheumatoid arthritis treatment. The use of gold containing drugs in the cure of cancer are then considered, with special emphasis to the use of nanoparticles and to the photo-thermal cancer therapy. The use of colloidal gold in diagnostics, introduced in the last decade is widely discussed. As a last point a survey on the adverse effects and on the toxicity of the various gold derivatives in use in medicine is presented. CONCLUSION: In this review, we described the surprisingly broad spectrum of possible uses of gold in diagnostics and in therapeutic approaches to multiple human diseases, ranging from degenerative to infectious diseases, and to cancer. In particular, gold nanoparticles appear as attractive elements in modern clinical medicine, combining high therapeutic properties, high selectivity in targeting cancer cells and low toxicity.


Assuntos
Artrite Reumatoide/tratamento farmacológico , Ouro/farmacologia , Neoplasias/tratamento farmacológico , Doenças Parasitárias/tratamento farmacológico , Viroses/tratamento farmacológico , Ouro/química , Humanos
13.
Acta Histochem ; 119(3): 228-234, 2017 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-28174028

RESUMO

The immunohistochemical expression of the calcium-binding protein calretinin during human cerebellar development has been investigated in this study. Human cerebellum samples, obtained from 7 fetuses and newborns ranging from 11 to 38 weeks of gestation, were 10% formalin-fixed, routinely processed and paraffin-embedded. 3µm-tick sections were immunostained with an anti-calretinin antibody. Our study evidenced a different immunoreactivity for calretinin in Purkinje cells and in several cerebellar interneurons at different intrauterine developmental stages. Whereas at 11 weeks of gestation calretinin immunoreactivity was not detected in the developing cerebellum, from the 18th to the 24th week, calretinin expression was found in Purkinje cells migrating from the ventricular neuroepithelium and in migrating cerebellar interneurons. From the 30th to the 38th week, calretinin was expressed by most of Purkinje cells and by migrating cerebellar interneurons. Furthermore, granule cells in the internal granular layer were also immunoreactive for calretinin. Our data show that calretinin, other than for developing Purkinje cells, is a useful marker also for migrating cerebellar interneurons and for some neuronal elements related to the granular layer. Moreover, given the critical role of calcium in a great variety of neuronal processes in the central nervous system, our findings suggest that calretinin may play a pivotal role in the regulation of neuronal excitability during intrauterine cerebellar development.


Assuntos
Calbindina 2/metabolismo , Cerebelo/crescimento & desenvolvimento , Cerebelo/metabolismo , Calbindina 2/química , Feto/química , Feto/metabolismo , Humanos , Imuno-Histoquímica , Células de Purkinje/metabolismo
14.
Biomed Res Int ; 2016: 3567275, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-27847811

RESUMO

Purpose. To investigate the effect of EPO administration on postresuscitation renal function. Methods. Twenty-four female Landrace/Large-White piglets aged 10-15 weeks with average weight of 19 ± 2 kg were randomly assigned to 2 different groups of 12 subjects each. After the end of an 8-minute ventricular fibrillation, the control group (Group C) received saline as placebo, whereas the EPO group (Group E) received EPO 5000 U/kg. The animals were resuscitated according to the 2010 European Resuscitation Council Guidelines for Resuscitation. Results. Five animals (41.67%) from Group C and 11 animals (91.67%) from Group E achieved ROSC (p = 0.027). Eight animals (66.67%, 5 surviving and 3 nonsurviving) from Group C suffered severe kidney damage or AKI compared to animals from Group E, in which none of the swine had evidence of severe kidney damage or AKI (p = 0.001). There was a statistically significant difference in all tested biochemical markers between the two groups, as well as a positive correlation of creatinine with NGAL, L-FABP, and IL-18 (summed mean values' p = 0.049, 0.01, and 0.004, resp.). Conclusions. Administration of EPO protected swine from postresuscitation acute kidney injury.


Assuntos
Lesão Renal Aguda , Eritropoetina/farmacologia , Rim/fisiopatologia , Ressuscitação/efeitos adversos , Fibrilação Ventricular/terapia , Lesão Renal Aguda/etiologia , Lesão Renal Aguda/fisiopatologia , Lesão Renal Aguda/prevenção & controle , Animais , Feminino , Rim/patologia , Suínos
15.
Birth Defects Res C Embryo Today ; 108(3): 207-223, 2016 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-27774781

RESUMO

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. Birth Defects Research (Part C) 108:207-223, 2016. © 2016 Wiley Periodicals, Inc.


Assuntos
Desenvolvimento Fetal/genética , Desenvolvimento Fetal/fisiologia , Transtornos Mentais/etiologia , Encéfalo/embriologia , Epigênese Genética , Epigenômica , Feminino , Feto , Humanos , Transtornos Mentais/embriologia , Neuropsiquiatria , Placenta , Gravidez , Efeitos Tardios da Exposição Pré-Natal/psicologia , Qualidade de Vida
16.
Arthritis Res Ther ; 18(1): 229, 2016 10 06.
Artigo em Inglês | MEDLINE | ID: mdl-27716395

RESUMO

BACKGROUND: In the present study, we investigated whether thymosin ß (Tß) in saliva and in minor salivary glands is differentially expressed in patients with primary Sjögren's syndrome (pSS) and patients with autoimmune diseases (systemic sclerosis [SSc], systemic lupus erythematosus [SLE], and rheumatoid arthritis [RA], with and without sicca syndrome [ss]). METHODS: Saliva specimens of nine patients with pSS, seven with ss/SSc, seven with ss/SLE, seven with ss/RA, seven with SSc, seven with SLE, and seven with RA, as well as ten healthy subjects, were analyzed using a high-performance liquid chromatograph coupled with a mass spectrometer equipped with an electrospray ionization source to investigate the presence and levels of Tß4, Tß4 sulfoxide, and Tß10. Immunostaining for Tß4 and Tß10 was performed on minor salivary glands of patients with pSS and ss. RESULTS: Tß4 levels were statistically higher in patients with pSS with respect to the other subgroups. Tß10 was detectable in 66.7 % of patients with pSS and in 42.8 % of those with ss/SSc, while Tß4 sulfoxide was detectable in 44.4 % of patients with pSS and in 42.9 % of those with ss/SSc. Tß10 and Tß4 sulfoxide were not detectable in patients without associated ss and in healthy control subjects. Regarding thymosin immunostaining, all patients had immunoreactivity for Tß10, and a comparable distribution pattern in the four different subgroups of patients was observed. Tß4 immunoreactivity was present in patients with ss/SSc and those with ss/SLE, while it was completely absent in patients with pSS and those with ss/RA. CONCLUSIONS: Our data show that higher salivary Tß expression characterizes patients with pSS, while Tß4 sulfoxide and Tß10 salivary expression was selectively present in patients with sicca symptoms. Moreover, at the immunohistochemical level in patients with pSS, minor salivary glands showed a peculiar pattern characterized by immunostaining for Tß10 in acinar cells in the absence of any reactivity for Tß4. These findings, taken together, suggest a different role for Tß4 and Tß10 in patients with pSS who have ss and other autoimmune disease.


Assuntos
Saliva/metabolismo , Glândulas Salivares Menores/metabolismo , Síndrome de Sjogren/metabolismo , Timosina/biossíntese , Idoso , Doenças Autoimunes/metabolismo , Cromatografia Líquida de Alta Pressão , Feminino , Humanos , Imuno-Histoquímica , Pessoa de Meia-Idade , Proteômica , Saliva/química , Espectrometria de Massas por Ionização por Electrospray
17.
Expert Rev Proteomics ; 13(9): 883-94, 2016 09.
Artigo em Inglês | MEDLINE | ID: mdl-27498711

RESUMO

INTRODUCTION: Care in pediatrics often refers to treatments directed to adults. However, childhood is a specific life period, with molecular pathways connected to development and thereby it requires distinctive considerations and special treatments under disease. Proteomics can help to elucidate the molecular mechanisms underlying the human development and disease onset in pediatric age and this review is devoted to underline the results recently obtained in the field. AREAS COVERED: The contribution of proteomics to the characterization of physiological modifications occurring during human development is presented. The proteomic studies carried out to elucidate the molecular mechanisms underlying different pediatric pathologies and to discover new markers for early diagnosis and prognosis of disease, comprising genetic and systemic pathologies, sepsis and pediatric oncology are thereafter reported. The investigations concerning milk composition in human and farm mammals are also presented. Finally, the chances offered by the integration of different -omic platforms are discussed. Expert commentary: The growing utilization of holistic technologies such as proteomics, metabolomics and microbiomics will allow, in the near future, to define at the molecular level the complexity of human development and related diseases, with great benefit for future generations.


Assuntos
Biomarcadores , Pediatria/tendências , Proteoma/genética , Proteômica , Adulto , Criança , Regulação da Expressão Gênica no Desenvolvimento/genética , Humanos , Metabolômica , Prognóstico
18.
Biomed Res Int ; 2016: 7261960, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-27504455

RESUMO

Aim. To evaluate the effects of erythropoietin administration on the adrenal glands in a swine model of ventricular fibrillation and resuscitation. Methods. Ventricular fibrillation was induced via pacing wire forwarded into the right ventricle in 20 female Landrace/Large White pigs, allocated into 2 groups: experimental group treated with bolus dose of erythropoietin (EPO) and control group which received normal saline. Cardiopulmonary resuscitation (CPR) was performed immediately after drug administration as per the 2010 European Resuscitation Council (ERC) guidelines for Advanced Life Support (ALS) until return of spontaneous circulation (ROSC) or death. Animals who achieved ROSC were monitored, mechanically ventilated, extubated, observed, and euthanized. At necroscopy, adrenal glands samples were formalin-fixed, paraffin-embedded, and routinely processed. Sections were stained with hematoxylin-eosin. Results. Oedema and apoptosis were the most frequent histological changes and were detected in all animals in the adrenal cortex and in the medulla. Mild and focal endothelial lesions were also detected. A marked interindividual variability in the degree of the intensity of apoptosis and oedema at cortical and medullary level was observed within groups. Comparing the two groups, higher levels of pathological changes were detected in the control group. No significant difference between the two groups was observed regarding the endothelial changes. Conclusions. In animals exposed to ventricular fibrillation, EPO treatment has protective effects on the adrenal gland.


Assuntos
Glândulas Suprarrenais/efeitos dos fármacos , Eritropoetina/administração & dosagem , Fibrilação Ventricular/tratamento farmacológico , Córtex Suprarrenal/efeitos dos fármacos , Medula Suprarrenal/efeitos dos fármacos , Animais , Apoptose/efeitos dos fármacos , Reanimação Cardiopulmonar/métodos , Modelos Animais de Doenças , Feminino , Substâncias Protetoras/administração & dosagem , Suínos
19.
Diagn Cytopathol ; 44(10): 783-6, 2016 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-27407066

RESUMO

BACKGROUND: Squamous intraepithelial lesions of the cervix uteri with eosinophilic features (eosinophilic dysplasia, ED) are a peculiar type of dysplasia with metaplastic phenotype which was described in histological specimens. The cytological features of these lesions have not been studied yet. METHODS: Histological samples from 66 women with features of ED and positive p16(INK4a) staining were included in the study. Within the previous year, all women had at least one pap-test, whose features were recorded and compared with 31 control samples with high-grade dysplasia of usual type. RESULTS: The previous pap-test showed high-grade dysplastic cells with non-hyperchromatic nuclei in 56/66 (84.8%) cases and metaplastic features in 60/66 (90.9%) cases. Conversely, the dysplastic cells of the usual lesions showed non-hyperchromatic nuclei in 6/31 (19.4%) and metaplastic features in 4/31 (12.9%) cases. Statistical analysis showed significant differences in distribution of the non-hyperchromatic nuclei (P < 0.001), metaplastic features (P < 0.001), presence of both non-hyperchromatic nuclei and metaplastic features (P < 0.001) and usual dysplastic features (P < 0.001) among the study and control groups. CONCLUSIONS: A high-grade squamous intraepithelial lesion with non-hyperchromatic nuclei or metaplastic features is often found in the pap-test previous to the histological diagnosis of ED and may represent the cytologic correlate of this particular type of dysplasia. Diagn. Cytopathol. 2016;44:783-786. © 2016 Wiley Periodicals, Inc.


Assuntos
Teste de Papanicolaou , Lesões Intraepiteliais Escamosas Cervicais/patologia , Estudos de Casos e Controles , Núcleo Celular/patologia , Cromatina/patologia , Eosinófilos/patologia , Feminino , Humanos
20.
J Urol ; 196(3): 911-8, 2016 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-27113968

RESUMO

PURPOSE: Among the different types of kidney stones, matrix stones are uncommon urinary calculi composed of a soft, pliable, amorphous substance with little crystalline content. To gain insight into the pathogenesis we investigated the protein component by analyzing the proteomic profiles of surgically removed matrix stones. MATERIALS AND METHODS: A total of 5 stones were harvested from 4 patients who underwent surgery for medical reasons at 3 clinical centers during a 7-year period. Matrix stone proteome characterization was performed by mass spectrometry based techniques using an integrated top-down/bottom-up proteomic platform. RESULTS: We identified 142 nonredundant proteins and peptides across all samples. Neutrophil defensin 1, and proteins S100-A8 and S100-A9 were the main components of these renal calculi. CONCLUSIONS: The abundance of identified inflammatory molecules points to an inflammatory process as the event that initializes soft calculi formation rather than as a consequence of such formation. The post-translational oxidative changes in S100-A8 and A9, and the presence of thymosin ß-4, granulins and ubiquitin also suggest the intervention of host defenses through a superimposed, vigorous counter inflammatory process. The post-translational changes seen in the proteins and peptides, and the known self-assembling capability of S100-A8 and S100-A9 probably explain the gelatinous consistency of these stones.


Assuntos
Calgranulina A/metabolismo , Calgranulina B/metabolismo , Inflamação/metabolismo , Proteômica/métodos , Cálculos Urinários/química , Cromatografia Líquida , Feminino , Seguimentos , Humanos , Imuno-Histoquímica , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Fatores de Tempo
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