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1.
Acta Diabetol ; 61(1): 63-68, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-37676288

RESUMO

AIMS: Periodical screening for diabetic retinopathy (DR) by an ophthalmologist is expensive and demanding. Automated DR image evaluation with Artificial Intelligence tools may represent a clinical and cost-effective alternative for the detection of retinopathy. We aimed to evaluate the accuracy and reliability of a machine learning algorithm. METHODS: This was an observational diagnostic precision study that compared human grader classification with that of DAIRET®, an algorithm nested in an electronic medical record powered by Retmarker SA. Retinal images were taken from 637 consecutive patients attending a routine annual diabetic visit between June 2021 and February 2023. They were manually graded by an ophthalmologist following the International Clinical Diabetic Retinopathy Severity Scale and the results were compared with those of the AI responses. The main outcome measures were screening performance, such as sensitivity and specificity and diagnostic accuracy by 95% confidence intervals. RESULTS: The rate of cases classified as ungradable was 1.2%, a figure consistent with the literature. DAIRET® sensitivity in the detection of cases of referable DR (moderate and above, "sight-threatening" forms of retinopathy) was equal to 1 (100%). The specificity, that is the true negative rate of absence of DR, was 80 ± 0.04. CONCLUSIONS: DAIRET® achieved excellent sensitivity for referable retinopathy compared with that of human graders. This is undoubtedly the key finding of the study and translates into the certainty that no patient in need of the ophthalmologist is misdiagnosed as negative. It also had sufficient specificity to represent a cost-effective alternative to manual grade alone.


Assuntos
Diabetes Mellitus , Retinopatia Diabética , Humanos , Retinopatia Diabética/diagnóstico , Inteligência Artificial , Reprodutibilidade dos Testes , Estudos de Viabilidade , Algoritmos , Programas de Rastreamento/métodos
2.
Eur Rev Med Pharmacol Sci ; 26(22): 8437-8443, 2022 11.
Artigo em Inglês | MEDLINE | ID: mdl-36459026

RESUMO

OBJECTIVE: Percutaneous mitral valve repair with the MitraClip system is an alternative procedure for high-risk patients not suitable for conventional surgery. The MitraClip can be safely performed under general anesthesia (GA) or deep sedation (DS) with spontaneous breathing using a combination of propofol and remifentanil. This study aimed to evaluate the benefits of target-controlled infusion (TCI) of remifentanil and administration of propofol during DS compared with manual administration of total intravenous anesthesia (TIVA) medication during GA in patients undergoing MitraClip. We assessed the impact of these procedures in terms of remifentanil dose, hemodynamic profile, adverse events, and days of hospital stay after the process. PATIENTS AND METHODS: From March 2013 to June 2015 (mean age 73.5 ± 9,54), patients underwent transcatheter MitraClip repair, 27 received DS via TCI and 27 GA with TIVA. RESULTS: Acute procedural success was 100%. DS-TCI group, in addition to a significant reduction of remifentanil dose administrated (249 µg vs. 2865, p < 0.01), resulted in a decrease in vasopressor drugs requirement for hemodynamic adjustments (29.6% vs. 63%, p = 0.03) during the procedure and a reduction of hypotension (p = 0.08). The duration of postoperative hospitalization did not differ between the two groups (5.4 days vs. 5.8 days, p = 0.4). CONCLUSIONS: Administration of remifentanil by TCI for DS in spontaneously breathing patients offers stable anesthesia conditions, with a lower amount of drugs, higher hemodynamic stability, and decreased side effects.


Assuntos
Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos , Hipotensão , Propofol , Humanos , Remifentanil , Anestesia Geral
3.
Nat Commun ; 13(1): 2642, 2022 05 12.
Artigo em Inglês | MEDLINE | ID: mdl-35550508

RESUMO

Cyclin-dependent kinase 12 (CDK12) overexpression is implicated in breast cancer, but whether it has a primary or only a cooperative tumorigenic role is unclear. Here, we show that transgenic CDK12 overexpression in the mouse mammary gland per se is sufficient to drive the emergence of multiple and multifocal tumors, while, in cooperation with known oncogenes, it promotes earlier tumor onset and metastasis. Integrative transcriptomic, metabolomic and functional data reveal that hyperactivation of the serine-glycine-one-carbon network is a metabolic hallmark inherent to CDK12-induced tumorigenesis. Consistently, in retrospective patient cohort studies and in patient-derived xenografts, CDK12-overexpressing breast tumors show positive response to methotrexate-based chemotherapy targeting CDK12-induced metabolic alterations, while being intrinsically refractory to other types of chemotherapy. In a retrospective analysis of hormone receptor-negative and lymph node-positive breast cancer patients randomized in an adjuvant phase III trial to 1-year low-dose metronomic methotrexate-based chemotherapy or no maintenance chemotherapy, a high CDK12 status predicts a dramatic reduction in distant metastasis rate in the chemotherapy-treated vs. not-treated arm. Thus, by coupling tumor progression with metabolic reprogramming, CDK12 creates an actionable vulnerability for breast cancer therapy and might represent a suitable companion biomarker for targeted antimetabolite therapies in human breast cancers.


Assuntos
Neoplasias da Mama , Animais , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/genética , Neoplasias da Mama/patologia , Carbono , Carcinogênese/genética , Quinases Ciclina-Dependentes/genética , Quinases Ciclina-Dependentes/metabolismo , Feminino , Ácido Fólico , Humanos , Metotrexato/uso terapêutico , Camundongos , Estudos Retrospectivos
4.
Arch Virol ; 166(2): 535-544, 2021 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-33403475

RESUMO

In vitro cell cultures are widely used models for dissecting cellular and molecular mechanisms that lead to certain physiological conditions and diseases. The pathogenesis of BoHV-4 in the bovine reproductive tract has been studied by conducting tests on primary cultures. However, many questions remain to be answered about the role of BoHV-4 in endometrial cells. The aim of this study was to compare the replication and gene expression of BoHV-4 in cell lines and bovine reproductive tract primary cells as an in vitro model for the study of this virus. We demonstrated that BoHV-4 strains differ in their in vitro growth kinetics and gene expression but have the same cell type preference. Our results demonstrate that BoHV-4 replicates preferentially in bovine endometrial cells (BEC). However, its replication capacity extends to various cell types, since all cells that were tested were permissive to BoHV-4 infection. The highest virus titers were obtained in BEC cells. Nevertheless, virus replication efficiency could not be fully predicted from the mRNA expression profiles. This implies that there are multiple cell-type-dependent factors and strain properties that determine the level of BoHV-4 replication. The results of this study provide relevant information about the in vitro behavior of two field isolates of BoHV-4 in different cell cultures. These findings may be useful for the design of future in vitro experiments to obtain reliable results not only about the pathogenic role of BoHV-4 in the bovine female reproductive tract but also in the development of efficient antiviral strategies.


Assuntos
Expressão Gênica/genética , Herpesvirus Bovino 4/genética , Replicação Viral/genética , Animais , Bovinos , Doenças dos Bovinos/virologia , Linhagem Celular , Endométrio/virologia , Feminino , Infecções por Herpesviridae/virologia , Humanos , RNA Mensageiro/genética , Carga Viral/genética
5.
Pancreatology ; 20(2): 193-198, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-31952917

RESUMO

BACKGROUND: Paraduodenal pancreatitis is a focal form of chronic pancreatitis that affects the groove area between the duodenum and the head of the pancreas. Consensus regarding surgical or nonsurgical management as the best treatment option is still lacking. METHODS: We retrospectively evaluated all patients managed for PP at The Pancreas Institute of the University Hospital Trust of Verona from 1990 to 2017. The outcomes of surgical vs. medical treatment with regard to pain control, quality of life and pancreatic insufficiency were evaluated through specific questionnaires. RESULTS: The final study population consisted of 75 patients: 62.6% underwent surgery, and 37.4% were managed without surgery. All surgical procedures consisted of pancreaticoduodenectomy. The median follow-up from the diagnosis of paraduodenal pancreatitis was 60 (12-240) months. Patients who underwent surgery experienced a similar incidence of steatorrhea (44.7 vs. 52.6%; p = 0.4) but a significantly higher incidence of diabetes (59.6 vs. 10.7%; p < 0.01) when compared to those managed without surgery. There was no difference in terms of reported chronic pain (Graded Chronic Pain Scale, median 0 vs. 1; p = 0.1) and quality of life (Pancreatitis QoL Instrument, median 82 vs. 79; p = 0.2). However, surgical patients reported a worse level of self-care activities associated with glycemic control (Diabetes Self-Management Questionnaire, median 20 vs. 28, p = 0.02). CONCLUSION: In patients affected by paraduodenal pancreatitis, surgery and medical therapy seem to obtain similar results in terms of quality of life and pain control. However, surgery is associated with an increased prevalence of postoperative diabetes with consequent relevant issues with self-care management. Surgery should be considered only in selected patients after adequate medical treatment.


Assuntos
Diabetes Mellitus/etiologia , Duodenopatias/cirurgia , Manejo da Dor/métodos , Pancreaticoduodenectomia/métodos , Pancreatite Crônica/cirurgia , Complicações Pós-Operatórias/epidemiologia , Qualidade de Vida , Adulto , Idoso , Idoso de 80 Anos ou mais , Diabetes Mellitus/psicologia , Duodenopatias/tratamento farmacológico , Duodenopatias/psicologia , Feminino , Controle Glicêmico , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Medição da Dor , Pancreatite Crônica/tratamento farmacológico , Pancreatite Crônica/psicologia , Complicações Pós-Operatórias/tratamento farmacológico , Complicações Pós-Operatórias/psicologia , Estudos Retrospectivos , Autocuidado , Esteatorreia/epidemiologia , Esteatorreia/etiologia , Inquéritos e Questionários
6.
Folia Biol (Praha) ; 66(4): 133-141, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33745260

RESUMO

Von Willebrand disease is a commonly inherited bleeding disorder caused by defects of von Willebrand factor (vWF). In the most common valve diseases, aortic valve stenosis (AVS) and mitral valve regurgitation (MVR), a bleeding tendency has been described in a number of patients. This has been associated to a high turbulence of blood flow through the compromised valve, promoting degradation of vWF with loss of high-molecular-weight multimers of vWF (HMWM), leading to an acquired von Willebrand syndrome (AvWS). We analysed three groups of patients, one affected by AVS, treated with transcatheter aortic valve implantation (TAVI), the second group of patients affected by MVR, treated with Mitraclip® mitral valve repair. The third group was represented by patients also affected by AVS, but not eligible for TAVI and treated with standard surgery. A fourth group of patients that underwent percutaneous coronary intervention (PCI) with stenting was used as a control. Our results demonstrated that the level of vWF measured as antigen concentration (vWF:Ag) increases in all cohorts of patients after treatment, while in control PCI patients, no modification of vWF:Ag has been registered. Western blot analysis showed only a quantitative loss of vWF in the pre-treatment time, but without significant HMWM modification. The monitoring of the vWF:Ag concentration, but not the quality of HMWM, can indicate the status of blood flow in the treated patients, thus introducing the possibility of using the vWF antigen detection in monitoring the status of replaced or repaired valves.


Assuntos
Estenose da Valva Aórtica/sangue , Insuficiência da Valva Mitral/sangue , Fator de von Willebrand/análise , Estenose da Valva Aórtica/diagnóstico , Humanos , Insuficiência da Valva Mitral/diagnóstico , Intervenção Coronária Percutânea , Plasma , Substituição da Valva Aórtica Transcateter , Doenças de von Willebrand
7.
Andrology ; 6(1): 192-198, 2018 01.
Artigo em Inglês | MEDLINE | ID: mdl-29145706

RESUMO

Oestrogen targeting in the human genital ducts is still not well-known. In fact, to date, the localization of oestrogen receptors, ESR1 and ESR2, is controversial and the presence of the membrane oestrogen receptor GPER (G protein-coupled oestrogen receptor) is unexplored. This study has investigated the expression of GPER, ESR1, ESR2 in human ductuli efferentes and proximal caput epididymis by immunohistochemistry and Western blot analysis. Furthermore, the presence of PELP1 (proline-glutamic acid-leucine-rich protein 1), a co-regulator of the oestrogen receptors, was also evaluated. In ductuli efferentes, GPER and ESR1 were clearly localized in all epithelial cells, while ESR2 was evidenced only in ciliated cells. Conversely, the epithelial cells of proximal caput epididymis revealed moderate GPER immunoreactivity, the absence of ERS1 and the occasional presence of ESR2. Furthermore, PELP1 was observed in ciliated cells of ductuli efferentes and in principal cells of proximal caput epididymis. Therefore, this study firstly demonstrated the expression of GPER in human male genital ducts, revealing a new mediator of oestrogen action in these anatomical sites. ESR1 and ESR2 were differentially localized in the two genital tracts together with PELP1, but cell sites of ERs and their co-regulator were not homogeneous. So, a different regional/cellular association of GPER with the classical oestrogen receptors was highlighted, suggesting that oestrogen action could be mediated by GPER, ESR1, ESR2 in ductuli efferentes, while by GPER and, occasionally by ESR2, in proximal caput epididymis. This study suggests that the specific oestrogen-mediated functions in human genital ducts might result from the different local interactions of oestrogens with oestrogen receptors and their co-regulators.


Assuntos
Epididimo/metabolismo , Receptor alfa de Estrogênio/biossíntese , Receptor beta de Estrogênio/biossíntese , Receptores de Estrogênio/biossíntese , Receptores Acoplados a Proteínas G/biossíntese , Ducto Deferente/metabolismo , Proteínas Correpressoras/biossíntese , Humanos , Masculino , Fatores de Transcrição/biossíntese
8.
Eur J Nutr ; 57(2): 679-688, 2018 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-28004268

RESUMO

PURPOSE: Proper evaluation of polyphenols intake at the population level is a necessary step in order to establish possible associations with health outcomes. Available data are limited, and so far no study has been performed in people with diabetes. The aim of this work was to document the intake of polyphenols and their major food sources in a cohort of people with type 2 diabetes and in socio-demographic subgroups. METHODS: We studied 2573 men and women aged 50-75 years. Among others, anthropometry was measured by standard protocol and dietary habits were investigated by food frequency questionnaire (EPIC). The intake of polyphenols was evaluated using US Department of Agriculture and Phenol-Explorer databases. RESULTS: The mean total polyphenol intake was 683.3 ± 5.8 mg/day. Non-alcoholic beverages represented the main food source of dietary polyphenols and provided 35.5% of total polyphenol intake, followed by fruits (23.0%), alcoholic beverages (14.0%), vegetables (12.4%), cereal products and tubers (4.6%), legumes (3.7%) and oils (2.1%); chocolate, cakes and nuts are negligible sources of polyphenols in this cohort. The two most important polyphenol classes contributing to the total intake were flavonoids (47.5%) and phenolic acids (47.4%). Polyphenol intake increased with age and education level and decreased with BMI; furthermore, in the northern regions of Italy, the polyphenol intake was slightly, but significantly higher than in the central or southern regions. CONCLUSIONS: The study documents for the first time the intake of polyphenols and their main food sources in people with diabetes using validated and complete databases of the polyphenol content of food. Compared with published data, collected in people without diabetes, these results suggest a lower intake and a different pattern of intake in people with diabetes.


Assuntos
Antioxidantes/administração & dosagem , Diabetes Mellitus Tipo 2/dietoterapia , Dieta para Diabéticos , Dieta Saudável , Flavonoides/administração & dosagem , Cooperação do Paciente , Fenóis/administração & dosagem , Idoso , Antioxidantes/análise , Bebidas/análise , Cinamatos/administração & dosagem , Cinamatos/análise , Estudos de Coortes , Estudos Transversais , Bases de Dados Factuais , Diabetes Mellitus Tipo 2/etnologia , Dieta para Diabéticos/etnologia , Dieta Saudável/etnologia , Feminino , Flavonoides/análise , Frutas/química , Glicosídeos/administração & dosagem , Glicosídeos/análise , Humanos , Itália , Masculino , Pessoa de Meia-Idade , Valor Nutritivo , Cooperação do Paciente/etnologia , Fenóis/análise , Polifenóis/administração & dosagem , Polifenóis/análise
9.
Front Pharmacol ; 8: 653, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-28974930

RESUMO

Drug-induced liver injury (DILI) is a major clinical problem where natural compounds hold promise for its abrogation. Khaya grandifoliola (Meliaceae) is used in Cameroonian traditional medicine for the treatment of liver related diseases and has been studied for its hepatoprotective properties. Till date, reports showing the hepatoprotective molecular mechanism of the plant are lacking. The aim of this study was therefore to identify compounds from the plant bearing hepatoprotective activity and the related molecular mechanism by assessing their effects against acetaminophen (APAP)-induced hepatotoxicity in normal human liver L-02 cells line. The cells were exposed to APAP (10 mM) or co-treated with phytochemical compounds (40 µM) over a period of 36 h and, biochemical and molecular parameters assessed. Three known limonoids namely 17-epi-methyl-6-hydroxylangolensate, 7-deacetoxy-7-oxogedunin and deacetoxy-7R-hydroxygedunin were identified. The results of cells viability and membrane integrity, reactive oxygen species generation and lipid membrane peroxidation assays, cellular glutathione content determination as well as expression of cytochrome P450 2E1 demonstrated the protective action of the limonoids. Immunoblotting analysis revealed that limonoids inhibited APAP-induced c-Jun N-terminal Kinase phosphorylation (p-JNK), mitochondrial translocation of p-JNK and Bcl2-associated X Protein, and the release of Apoptosis-inducing Factor into the cytosol. Interestingly, limonoids increased the expression of Mitogen-activated Protein Kinase Phosphatase (Mkp)-1, an endogenous inhibitor of JNK phosphorylation and, induced the nuclear translocation of Nuclear Factor Erythroid 2-related Factor-2 (Nrf2) and decreased the expression of Kelch-like ECH-associated Protein-1. The limonoids also reversed the APAP-induced decreased mRNA levels of Catalase, Superoxide Dismutase-1, Glutathione-S-Transferase and Methionine Adenosyltransferase-1A. The obtained results suggest that the isolated limonoids protect L-02 hepatocytes against APAP-induced hepatotoxicity mainly through increase expression of Mkp-1 and nuclear translocation of Nrf2. Thus, these compounds are in part responsible of the hepatoprotective activity of K. grandifoliola and further analysis including in vivo and toxicological studies are needed to select the most potent compound that may be useful as therapeutic agents against DILI.

10.
Eur J Obstet Gynecol Reprod Biol ; 218: 99-105, 2017 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-28963923

RESUMO

OBJECTIVE: The study aimed to explore the type 1 and type 2 cytokines expression in the endometrium from women affected by endometriosis compared to controls. The expression of TSG-6, a multifunctional protein involved in several inflammatory disease, was also evaluated. Study Design SETTING: Experimental clinical study. PATIENTS: 10 patients affected by endometriosis and 11 controls. INTERVENTIONS: Patients underwent to an ultrasound transvaginal examination and a diagnostic hysteroscopy in order to exclude any uterine abnormality. All patients underwent endometrial biopsy using a Novak's curette. MAIN OUTCOME MEASURES: The endometrial expression of type 1 (IL- 1 ß TNF-α, IL-8) and type 2 (IL-10) cytokines, and of TSG-6 was evaluated by immunohistochemistry and by real time PCR. The expression of TSG-6 was confirmed by western blot. RESULTS: Results of PCR analysis and of immunohistochemistry revealed an increased expression of IL-1ß, TNF-α, IL-8 and of TSG-6 in the endometrium of endometriosic patients. IL-10 expression did not show any difference. CONCLUSIONS: An increased expression of pro-inflammatory type 1 cytokines was demonstrated in the endometrium from endometriosic patients, suggesting an endometrial environment harmful for implantation due to the prevalence of Th1 related immunity. An increased expression of TSG-6 was also demonstrated for the first time. Our findings concur to better define the inflammatory imbalance and the abnormal endometrial receptivity, reported in literature, of the eutopic endometrium of women affected by endometriosis.


Assuntos
Endometriose/metabolismo , Endométrio/metabolismo , Infertilidade Feminina/imunologia , Adulto , Western Blotting , Estudos de Casos e Controles , Moléculas de Adesão Celular/genética , Moléculas de Adesão Celular/metabolismo , Endométrio/citologia , Feminino , Regulação da Expressão Gênica , Humanos , Mediadores da Inflamação/imunologia , Interleucina-10/metabolismo , Interleucina-1alfa/genética , Interleucina-1alfa/metabolismo , Interleucina-1beta/metabolismo , Interleucina-8/metabolismo , RNA Mensageiro/metabolismo , Reação em Cadeia da Polimerase em Tempo Real , Fator de Necrose Tumoral alfa/genética , Fator de Necrose Tumoral alfa/metabolismo , Ultrassonografia , Adulto Jovem
11.
G Chir ; 38(1): 33-36, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-28460201

RESUMO

Sternal Wound Infections (SWI) represent a dangerous complication after cardiac surgery entailing significantly longer hospital stays and worse short-term survival, especially in case of deep infections (DSWI) with the onset of osteomielitis or mediastinitis. The real incidence of SWI can be estimated between 0.25% and 10%; among the risk factors for sternal dehiscences after a longitudinal median sternotomy, several experiences underline the role of diabetes as an independent risk factor for post-operative infections, especially in patients affected by COPD with higher BMI. The application of a negative-pressure therapy, through instill modality too, assures a wound cleansing through periodic irrigation of topical solutions with particulate secretion removal; moreover it improves the granulation process owing to the increased blood flow and makes the size wound reduction easier, representing very often the treatment of first-line in DSWI and an optimal bridge for another reconstructive procedure of the sternal defect. The following case report shows how a plastic surgical approach associated to the adoption of a VAC-therapy instill after specific antibiotictherapy has integrated and optimized the trend of a very complex clinical circumstance.


Assuntos
Procedimentos Cirúrgicos Cardíacos , Esternotomia/efeitos adversos , Esterno/cirurgia , Infecção da Ferida Cirúrgica/etiologia , Idoso , Procedimentos Cirúrgicos Cardíacos/métodos , Feminino , Humanos , Tratamento de Ferimentos com Pressão Negativa , Procedimentos de Cirurgia Plástica , Índice de Gravidade de Doença , Infecção da Ferida Cirúrgica/patologia , Infecção da Ferida Cirúrgica/terapia
12.
Cell Death Differ ; 23(9): 1502-14, 2016 09 01.
Artigo em Inglês | MEDLINE | ID: mdl-27058317

RESUMO

Newly generated neurons pass through a series of well-defined developmental stages, which allow them to integrate into existing neuronal circuits. After exit from the cell cycle, postmitotic neurons undergo neuronal migration, axonal elongation, axon pruning, dendrite morphogenesis and synaptic maturation and plasticity. Lack of a global metabolic analysis during early cortical neuronal development led us to explore the role of cellular metabolism and mitochondrial biology during ex vivo differentiation of primary cortical neurons. Unexpectedly, we observed a huge increase in mitochondrial biogenesis. Changes in mitochondrial mass, morphology and function were correlated with the upregulation of the master regulators of mitochondrial biogenesis, TFAM and PGC-1α. Concomitant with mitochondrial biogenesis, we observed an increase in glucose metabolism during neuronal differentiation, which was linked to an increase in glucose uptake and enhanced GLUT3 mRNA expression and platelet isoform of phosphofructokinase 1 (PFKp) protein expression. In addition, glutamate-glutamine metabolism was also increased during the differentiation of cortical neurons. We identified PI3K-Akt-mTOR signalling as a critical regulator role of energy metabolism in neurons. Selective pharmacological inhibition of these metabolic pathways indicate existence of metabolic checkpoint that need to be satisfied in order to allow neuronal differentiation.


Assuntos
Diferenciação Celular , Engenharia Metabólica , Neurônios/metabolismo , Animais , Diferenciação Celular/fisiologia , DNA Mitocondrial/metabolismo , Glucose/metabolismo , Transportador de Glucose Tipo 3/metabolismo , Glutamato-Cisteína Ligase/deficiência , Glutamato-Cisteína Ligase/genética , Ácido Glutâmico/metabolismo , Glutamina/metabolismo , Camundongos , Camundongos Knockout , Microscopia Eletrônica de Transmissão , Mitocôndrias/genética , Mitocôndrias/metabolismo , Neurônios/citologia , Coativador 1-alfa do Receptor gama Ativado por Proliferador de Peroxissomo/metabolismo , Fosfatidilinositol 3-Quinases/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Transdução de Sinais , Serina-Treonina Quinases TOR/metabolismo
13.
Andrology ; 4(1): 121-7, 2016 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-26714890

RESUMO

Estrogens are involved in growth, differentiation and pathogenesis of human prostate through the mediation of the classical estrogen receptors ERα and ERß. The G protein-coupled estrogen receptor (GPER) is a 'novel' mediator of estrogen signaling which has been recently recognized in some human reproductive tissues, but its expression in the prostate gland is still unknown. Here, we investigated GPER in benign (from 5 patients) and neoplastic prostatic tissues (from 50 patients) by immunohistochemical analysis and Western blotting. Normal areas of benign prostates revealed a strong GPER immunoreactivity in the basal epithelial cells while luminal epithelial cells were unreactive and stromal cells were weakly immunostained. GPER was also immunolocalized in adenocarcinoma samples but the immunoreactivity of tumoral areas decreased from Gleason pattern 2 to Gleason pattern 4. Furthermore, a strong GPER immunostaining was also revealed in cells of pre-neoplastic lesions (high-grade prostatic intra-epithelial neoplasia). Western blot analysis of benign and tumor protein extracts showed the presence of a ~42 kDa band, consistent with the GPER molecular weight. An increase in both pAkt and p cAMP-response-binding protein (pCREB) levels was also observed in poorly differentiated PCa samples. Finally, this work identified GPER in the epithelial basal cells of benign human prostate, with a different localization with respect to the classical estrogen receptors. Furthermore, the expression of GPER in prostatic adenocarcinoma cells was also observed but with a modulation of the immunoreactivity according to tumor cell arrangements.


Assuntos
Adenocarcinoma/patologia , Células Epiteliais/metabolismo , Epitélio/metabolismo , Próstata/metabolismo , Neoplasias da Próstata/patologia , Receptores de Estrogênio/metabolismo , Receptores Acoplados a Proteínas G/metabolismo , Idoso , Diferenciação Celular , Proteína de Ligação ao Elemento de Resposta ao AMP Cíclico/metabolismo , Estrogênios/metabolismo , Humanos , Masculino , Pessoa de Meia-Idade , Proteínas Proto-Oncogênicas c-akt/metabolismo , Transdução de Sinais
15.
Endoscopy ; 44(1): 27-31, 2012 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-22125197

RESUMO

BACKGROUND: Cold polypectomy techniques (without electrocautery) by means of biopsy forceps or snare are widely adopted for the removal of subcentimetric polyps. However, few data are available on the safety of this approach. The aim of this study was to assess the safety of cold polypectomy for subcentimetric polyps, as well as the rate of advanced neoplasia in these lesions. PATIENTS AND METHODS: In a prospective multicenter trial, consecutive patients with at least one < 10-mm polyp at colonoscopy were prospectively included. All of the < 10-mm polyps detected within the study period were removed by cold polypectomy. The rates of immediate or delayed bleeding and other complications were assessed at 7 and 30 days after cold polypectomy by telephone calls. The rate of advanced histology was also assessed. Predictive variables of postpolypectomy bleeding or advanced neoplasia were identified by multivariate analysis. RESULTS: A total of 1015 < 10-mm polyps in 823 patients (15.5 % on antiplatelet agents) were removed. Of these, 822 (81 %) were ≤ 5 mm and 193 (19 %) were 6 - 9 mm. Immediate postpolypectomy bleeding occurred in 18 patients, corresponding to a per-patient and per-polyp bleeding rate of 2.2 % (95 % confidence interval [CI] 1.2 % - 3.2 %) and 1.8 % (95 %CI 1 % - 2.6 %), respectively. Therapy with antiplatelet agents (odds ratio [OR] 4; 95 %CI 1.5 - 10.6) and larger polyp size (OR 2; 95 %CI 1.1 - 6.9) were independent predictors of bleeding. Bleeding was successfully treated by endoscopic hemostasis in all cases and required no further medical intervention. Advanced neoplasia prevalence in polyps ≤ 5 mm was as high as 8.7 %. CONCLUSIONS: The results from this study showed the high safety of a cold polypectomy approach for subcentimetric polyps. This was due to the low rate of postpolypectomy bleeding and to the high efficacy of endoscopic hemostasis in its treatment. The high rate of advanced neoplasia in polyps ≤ 5 mm should prompt some caution on the management of these lesions following detection at computed tomography colonography or colon capsule endoscopy.


Assuntos
Neoplasias do Colo/diagnóstico , Pólipos do Colo/cirurgia , Hemorragia Gastrointestinal/etiologia , Hemorragia Pós-Operatória/etiologia , Idoso , Perda Sanguínea Cirúrgica , Neoplasias do Colo/patologia , Pólipos do Colo/patologia , Colonoscopia , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Inibidores da Agregação Plaquetária/efeitos adversos , Fatores de Risco
16.
Gene ; 487(2): 129-34, 2011 Nov 10.
Artigo em Inglês | MEDLINE | ID: mdl-21839814

RESUMO

Periostin (POSTN), an osteoblast-specific secreted protein known to be associated with cell adhesion activity for bone formation and development by the epithelial cell-derived tumors, leads to a significant enhancement in angiogenesis and tumorigenesis. At present, little is known about the mechanisms underlying its transcriptional control either in physiological or neoplastic conditions. In this study we demonstrate that the ability of the human POSTN promoter to drive transcription mostly depends on the activity of YingYang-1 (YY1) zinc finger transcription factor. YY1, whose regulatory role in biology includes, besides transcriptional control, also chromatin remodeling, DNA damage repair and tumorigenesis, acts as a strong negative modulator of the POSTN expression. We retain that the identification of the functional role of YY1 in the transcriptional control of the human POSTN gene adds new insights in the studies focused on gene expression in normal and transformed cells.


Assuntos
Moléculas de Adesão Celular/genética , Transcrição Gênica , Fator de Transcrição YY1/fisiologia , Sequência de Bases , Sítios de Ligação/genética , Moléculas de Adesão Celular/metabolismo , Células Cultivadas , Regulação para Baixo/genética , Inativação Gênica/fisiologia , Células HeLa , Humanos , Dados de Sequência Molecular , Regiões Promotoras Genéticas , Ligação Proteica/fisiologia , Transcrição Gênica/genética , Transfecção , Fator de Transcrição YY1/genética , Fator de Transcrição YY1/metabolismo
17.
Endoscopy ; 42(7): 532-5, 2010 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-20593330

RESUMO

BACKGROUND AND STUDY AIM: Endoscopic treatment of Zenker's diverticulum has been successfully reported over the last 10 years using different approaches. The hook-knife is a new device originally developed for endoscopic submucosal dissection procedures. This study aimed to investigate the safety and efficacy of endoscopic myotomy performed with the hook-knife. PATIENTS AND METHOD: From July 2005, 32 consecutive patients (23-male, mean age 74.8 years) with dysphagia secondary to the presence of Zenker's diverticulum were prospectively enrolled. Myotomy was performed using a straight-end transparent hood to the tip of the scope and the hook-knife for the incision of the bridge between the Zenker's diverticulum and the esophagus. Clinical outcome was evaluated assigning a dysphagia symptom score from 0 (symptoms absent) to 4 (inability to swallow saliva). RESULTS: General anesthesia was used in 4 patients, deep sedation with propofol in 23 patients, while midazolam was used in 5 patients. The mean procedural time was 28 minutes. Complications occurred in 2 patients (6.25 %). At 1 month follow-up, the mean dysphagia score was significantly improved from 2.9 to 0.6 ( P < 0.001) with 87.5 % of patients free of symptoms and 4 patients with dysphagia that was persistent but milder than before the treatment. Three of these 4 patients underwent a successful second endoscopic treatment with complete relief of dysphagia; one was not re-treated because of advanced age (92 years). During the follow-up period (23.87 +/- 9.6 months), 2 patients developed dysphagia recurrence. The overall success rate was 90.6 %. CONCLUSIONS: Diverticulectomy with a flexible scope and the hook-knife may represent a safe and effective alternative treatment for patients with Zenker's diverticulum.


Assuntos
Transtornos de Deglutição/terapia , Esofagoscopia/métodos , Divertículo de Zenker/terapia , Idoso , Idoso de 80 Anos ou mais , Transtornos de Deglutição/etiologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Resultado do Tratamento , Divertículo de Zenker/complicações
18.
J Neurosurg Sci ; 53(2): 59-61, 2009 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-19546845

RESUMO

Spontaneous spinal extradural hematoma is a rare clinical entity, commonly associated with coagulopathies, tumours or vascular malformations. They are often a neurosurgical emergency, therefore prompt diagnosis and early treatment are necessary. The Cobb syndrome is a neurocutaneous syndrome in which there are metameric vascular skin nevus and spinal arteriovenous malformation. The authors report the case of a 52-year-old woman with acute cervical myelopathy and a cervical cutaneous hemangioma on clinical examination. It is stressed the importance of clinical suspicion of cutaneo-meningospinal angiomatosis based on a spinal cord syndrome in the presence of a vascular skin nevus of the same metameric level.


Assuntos
Angiomatose/complicações , Malformações Arteriovenosas/complicações , Hematoma Epidural Craniano/etiologia , Nevo/complicações , Neoplasias Cutâneas/complicações , Angiomatose/patologia , Angiomatose/cirurgia , Malformações Arteriovenosas/patologia , Malformações Arteriovenosas/cirurgia , Feminino , Hematoma Epidural Craniano/patologia , Hematoma Epidural Craniano/cirurgia , Humanos , Imageamento por Ressonância Magnética , Pessoa de Meia-Idade , Nevo/patologia , Nevo/cirurgia , Neoplasias Cutâneas/patologia , Neoplasias Cutâneas/cirurgia
19.
Minerva Cardioangiol ; 57(1): 57-75, 2009 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-19202519

RESUMO

The exponential growth of percutaneous coronary intervention (PCI) has in large part been due to expansion of the indications to include the procedure in patients with extensive coronary disease, multiple risk factors, older age and comorbidities. Improvement in PCI equipment, development of new interventional techniques, and availability of myocardial and systemic support techniques have all contributed to this growth. With these advances, patients once considered high risk for PCI are no longer considered high risk. This article reviews the complex coronary lesions challenges, various interventional and pharmacologic strategies for optimal results and novel technology.


Assuntos
Angioplastia Coronária com Balão/métodos , Doença da Artéria Coronariana/terapia , Stents , Ensaios Clínicos como Assunto , Ponte de Artéria Coronária/métodos , Doença da Artéria Coronariana/patologia , Medicina Baseada em Evidências , Humanos , Ensaios Clínicos Controlados Aleatórios como Assunto , Medição de Risco , Fatores de Risco , Veia Safena/transplante , Resultado do Tratamento
20.
Surg Endosc ; 23(5): 1065-9, 2009 May.
Artigo em Inglês | MEDLINE | ID: mdl-18830754

RESUMO

BACKGROUND: Endoscopic mucosal resection (EMR) is today the treatment of choice for flat and sessile colorectal lesion, the only concern being completeness of resection. One of the major issues is the choice of the infiltrating substance to enable a long-lasting cushion under the lesion. The aim of this study was to prospectively evaluate safety and efficacy of hydroxy-propyl-methyl-cellulose (HPMC) injection for this purpose. PATIENTS: All flat and sessile lesions of the colon and rectum larger than 20 mm and considered suitable for EMR were included. In all cases 0.8% HPMC solution was injected through a 23G needle, in quantity according to the endoscopist's indication. Primary endpoints of the study were: (1) ability to perform en bloc resection of the lesions by using this new injection means, (2) complete resection rate, and (3) early and late complication rate. RESULTS: We resected 27 flat, sessile, or laterally spreading lesions up to 60 mm (28 mm average). Mean dose of HPMC injected was 10.2 ml (range 8-40 ml). Median procedure time was 32 min (range 15-105 min). En bloc resection was achieved in up to 21 cases (78%). Histologically detected complete tumour removal was achieved in 23 lesions, whereas lateral margins could not be properly evaluated in 4 cases due to coagulation artefacts. No perforation was observed. Procedural spurting bleeding was managed by epinephrine injection in one case and clip application in the remaining. Two case of local recurrence of adenomatous tissue were observed at 3 and 12 months, and treated by EMR. No complication related to the use of HPMC was observed. CONCLUSIONS: Injection of HPMC for EMR resulted safe and effective, allowing en bloc resection in the majority of cases with a limited number of complications. Continued progress in the field will include more outcomes research and techniques simplification.


Assuntos
Pólipos Intestinais/terapia , Metilcelulose/análogos & derivados , Soluções Farmacêuticas/administração & dosagem , Idoso , Idoso de 80 Anos ou mais , Pólipos do Colo/terapia , Colonoscopia , Dissecação , Feminino , Humanos , Derivados da Hipromelose , Masculino , Metilcelulose/administração & dosagem , Pessoa de Meia-Idade , Doenças Retais/terapia , Resultado do Tratamento
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