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1.
Drug Chem Toxicol ; 47(1): 60-66, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-36912201

RESUMO

Endocrine disruptors, such as estrogen, are chemical substances with the potential to alter the hormonal balance of organisms. Their origin can be natural or artificial, and they can act at very low doses. The estrogen 17α-ethinylestradiol (EE2) is used worldwide as an oral contraceptive and is a potential contaminant in aquatic ecosystems. It is well documented that these environmental pollutants can act directly or indirectly on the reproductive system, impairing development and fertility. However, little is known about the alteration of the cell oxidative status induced by EE2. The main objective of this study was to evaluate the effect on the gill cells of adult zebrafish exposed in vivo to EE2, analyzing cell histology, DNA damage and the expression levels of genes encoding the main enzymes involved in oxidative stress pathways. The histological study showed that EE2 produces moderate to high damage to the gill tissue, an increase in gill cell DNA damage and the mRNA levels of the genes corresponding to the manganese superoxide dismutase (Mn-sod) and catalase (cat) after exposure to 5 ng/L EE2. The results indicate that EE2 causes tissue alterations, DNA damage and oxidative stress. EE2 produced important alterations in the gills, a fundamental organ for the survival of fish. There is a clear need for further research on the ecological consequences of EDCs on non-target organisms.


Assuntos
Poluentes Químicos da Água , Peixe-Zebra , Animais , Peixe-Zebra/genética , Antioxidantes/farmacologia , Brânquias , Ecossistema , Etinilestradiol/toxicidade , Estrogênios/farmacologia , Dano ao DNA , Poluentes Químicos da Água/toxicidade
2.
Clin Oncol (R Coll Radiol) ; 35(6): e362-e375, 2023 06.
Artigo em Inglês | MEDLINE | ID: mdl-36967312

RESUMO

AIMS: Understanding the correlations between underlying medical and personal characteristics of a patient with cancer and the risk of lung metastasis may improve clinical management and outcomes. We used machine learning methodologies to predict the risk of lung metastasis using readily available predictors. MATERIALS AND METHODS: We retrospectively analysed a cohort of 11 164 oncological patients, with clinical records gathered between 2000 and 2020. The input data consisted of 94 parameters, including age, body mass index (BMI), sex, social history, 81 primary cancer types, underlying lung disease and diabetes mellitus. The strongest underlying predictors were discovered with the analysis of the highest performing method among four distinct machine learning methods. RESULTS: Lung metastasis was present in 958 of 11 164 oncological patients. The median age and BMI of the study population were 63 (±19) and 25.12 (±5.66), respectively. The random forest method had the most robust performance among the machine learning methods. Feature importance analysis revealed high BMI as the strongest predictor. Advanced age, smoking, male gender, alcohol dependence, chronic obstructive pulmonary disease and diabetes were also strongly associated with lung metastasis. Among primary cancers, melanoma and renal cancer had the strongest correlation. CONCLUSIONS: Using a machine learning-based approach, we revealed new correlations between personal and medical characteristics of patients with cancer and lung metastasis. This study highlights the previously unknown impact of predictors such as obesity, advanced age and underlying lung disease on the occurrence of lung metastasis. This prediction model can assist physicians with preventive risk factor control and treatment strategies.


Assuntos
Diabetes Mellitus , Neoplasias Pulmonares , Humanos , Masculino , Estudos Retrospectivos , Fatores de Risco , Diabetes Mellitus/epidemiologia
3.
Sci Rep ; 11(1): 10139, 2021 05 12.
Artigo em Inglês | MEDLINE | ID: mdl-33980934

RESUMO

Post-operative cognitive dysfunction (POCD) is a debilitating clinical phenomenon in elderly patients. Management of pain in elderly is complicated because analgesic opiates elicit major side effects. In contrast, paracetamol (acetaminophen) has shown analgesic efficacy, no impact on cognition, and its side effects are well tolerated. We investigated the efficacy of paracetamol, compared to the opioid analgesic buprenorphine, in a model of POCD by investigating cognitive decline, allodynia, peripheral and hippocampal cytokines levels, and hippocampal microtubule dynamics as a key modulator of synaptic plasticity. A POCD model was developed in middle-aged (MA) rats by inducing a tibia fracture via orthopaedic surgery. Control MA rats did not undergo any surgery and only received isoflurane anaesthesia. We demonstrated that cognitive decline and increased allodynia following surgery was prevented in paracetamol-treated animals, but not in animals which were exposed to anesthesia alone or underwent the surgery and received buprenorphine. Behavioral alterations were associated with different peripheral cytokine changes between buprenorphine and paracetamol treated animals. Buprenorphine showed no central effects, while paracetamol showed modulatory effects on hippocampal cytokines and markers of microtubule dynamics which were suggestive of neuroprotection. Our data provide the first experimental evidence corroborating the use of paracetamol as first-choice analgesic in POCD.


Assuntos
Acetaminofen/farmacologia , Disfunção Cognitiva/tratamento farmacológico , Citoesqueleto/metabolismo , Complicações Cognitivas Pós-Operatórias/tratamento farmacológico , Complicações Cognitivas Pós-Operatórias/metabolismo , Fatores Etários , Analgésicos/farmacologia , Anestésicos , Animais , Cognição/efeitos dos fármacos , Citocinas/metabolismo , Gerenciamento Clínico , Modelos Animais de Doenças , Suscetibilidade a Doenças , Hipocampo/efeitos dos fármacos , Hipocampo/metabolismo , Hipocampo/fisiopatologia , Projetos Piloto , Complicações Cognitivas Pós-Operatórias/etiologia , Ratos
4.
Ann Oncol ; 31(12): 1755-1763, 2020 12.
Artigo em Inglês | MEDLINE | ID: mdl-32979511

RESUMO

BACKGROUND: Initial studies of preoperative checkpoint inhibition before radical cystectomy (RC) have shown promising pathologic complete responses. We aimed to analyze the survival outcomes of patients enrolled in the PURE-01 study (NCT02736266). PATIENTS AND METHODS: We report the results of the secondary end points of PURE-01 in the final population of 143 patients. In particular, we report the event-free survival (EFS) outcomes, defined as the time from the first cycle of pembrolizumab to radiographic disease progression precluding RC, initiation of neoadjuvant chemotherapy (NAC), recurrence after RC, or death from any cause. Other end points were recurrence-free survival (RFS) and overall survival (OS). Subgroup analyses were carried out, including pathological response category, clinical complete responses (CR) assessed via multiparametric magnetic resonance imaging (mpMRI), and molecular subtyping. Cox regression analyses for EFS were also carried out. RESULTS: After a median [interquartile range (IQR)] follow-up of 23 (15-29) months, 12- and 24-month EFS were 84.5% [95% confidence interval (CI): 78.5-90.9] and 71.7% (62.7-82). The prognosis was favorable across all the different pathological response subgroups, with the exception of ypN+ (N = 21), showing a 24-month RFS (95% CI) of 39.3% (19.2% to 80.5%). A statistically significant EFS benefit was observed in patients with a clinical CR (P = 0.002). Programmed cell-death-ligand-1 combined positive score was significantly associated with longer EFS in multivariable analyses. Four patients refused RC after clinical evidence of CR, and none of them have recurred after a median follow-up of 10 months (IQR: 11-15). The claudin-low subtype displayed a numerically longer EFS after pembrolizumab and RC compared with the other subtypes. CONCLUSIONS: The EFS results from PURE-01 revealed that the immunotherapy effect was maintained post-RC in most patients. Pembrolizumab compared favorably with neoadjuvant chemotherapy, irrespective of the biomarker status. Molecular subtyping may be a useful tool to select the patients who are predicted to benefit the most from neoadjuvant pembrolizumab.


Assuntos
Cistectomia , Neoplasias da Bexiga Urinária , Anticorpos Monoclonais Humanizados , Quimioterapia Adjuvante , Intervalo Livre de Doença , Humanos , Terapia Neoadjuvante , Recidiva Local de Neoplasia/tratamento farmacológico , Estudos Retrospectivos , Resultado do Tratamento , Neoplasias da Bexiga Urinária/tratamento farmacológico , Neoplasias da Bexiga Urinária/cirurgia
5.
J Comp Pathol ; 179: 65-73, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-32958150

RESUMO

We document the causes and pathological findings in 50 cases of equine pneumonia and pleuritis in Southern Brazil. Suppurative (17/50), pyogranulomatous (14/50), aspiration (5/50), mycotic (4/50), bronchointerstitial (3/50), embolic (3/50) and eosinophilic granulomatous pneumonia (1/50) and pleuritis (3/50) were the main conditions identified. Streptococcus spp. were identified in 11 cases of suppurative pneumonia. Suppurative pneumonia was further divided into acute (8/17), subacute (6/17) and chronic (3/17) based on the morphological pattern of lesions. Rhodococcus equi was identified in all cases of pyogranulomatous pneumonia and exclusively affected young foals.


Assuntos
Doenças dos Cavalos/microbiologia , Pleurisia/veterinária , Pneumonia/veterinária , Animais , Brasil , Cavalos
6.
Artigo em Inglês | MEDLINE | ID: mdl-32613093

RESUMO

INTRODUCTION: This survey describes Italian RTTs' involvement and opinions in research activities related to radiation oncology. Primary aim was to assess the degree of involvement of the national RTTs community in research and to describe how RTTs can integrate their skills collaborating with other professionals. MATERIALS AND METHODS: A ten-items multiple-choice questionnaire, with 2-8 possible responses, was developed by a steering committee and generated on a survey platform. Links were sent via email to Italian RTTs.The questions were divided in 3 domains: demographic data; scientific research and activity; opinions about RTTs role in scientific research. The survey started on October 1, 2018 and ended on January 31, 2019. RESULTS: One hundred thirty-five out of 509 (26.5%) RTTs responded to the questionnaire at its expiring date; 97.73% think to be valid contributors in radiation oncology research, expressing clear interest in "data collection" tasks (52.71%); 38.64% feel unsupported by other professionals in the research team and 59.85% of the respondents are not members in any scientific society. CONCLUSIONS: The role of Italian RTTs in research is heterogeneous. Mainly RTTs in the age range from 30 to 40 years responded to the survey showing their interest in scientific research. This might be related to different informatics and educational skills as well as to personal attitudes. RTTs particular skills, like data management and technical hypothesis generation abilities, are of benefit to realize research projects. Therefore, engaging RTTs in research activities is strongly suggested.

7.
Neuropharmacology ; 164: 107897, 2020 03 01.
Artigo em Inglês | MEDLINE | ID: mdl-31794725

RESUMO

Mutations in the X-linked cyclin-dependent kinase-like 5 (CDKL5) gene are responsible for the onset of CDKL5 Deficiency Disorder (CDD), a neurological pathology characterised by severe infantile seizures, intellectual disability, impairment of gross motor skills, sleep and gastrointestinal disturbances. CDKL5 is a serine/threonine kinase the molecular network of which is not yet fully understood. Loss of CDKL5 both in vitro and in vivo leads to altered neuronal morphology including axon specification and outgrowth, dendritic arborisation and spine morphology suggesting a link between CDKL5 and the regulation of proper cytoskeleton functioning. Recently, we found that CDKL5 regulates the binding of CLIP170 to microtubules (MT). CLIP170 is a MT-plus end tracking protein (+TIP) that associates with MTs when present in its open, active conformation. Here we present evidence suggesting CLIP170 contributes to neuronal CDKL5-dependent defects and that it represents an important novel druggable target for CDD; indeed, CLIP170 is directly targeted by the neuroactive steroid pregnenolone (PREG), which induces the active conformation of the protein thus promoting MT-dynamics. We here show that PREG and a synthetic derivative pregnenolone-methyl-ether (PME) can restore the MT association of CLIP170 and revert morphological and molecular defects in Cdkl5-KO neurons at different stages of maturation. All together, these findings identify CLIP170 as possible novel druggable target for CDKL5 related disorders providing an intriguing prospective for future disease-modifying drug-based therapies.


Assuntos
Síndromes Epilépticas/tratamento farmacológico , Síndromes Epilépticas/genética , Pregnenolona/uso terapêutico , Espasmos Infantis/tratamento farmacológico , Espasmos Infantis/genética , Animais , Axônios/efeitos dos fármacos , Axônios/ultraestrutura , Células COS , Chlorocebus aethiops , Ensaio Cometa , Dendritos/efeitos dos fármacos , Dendritos/ultraestrutura , Proteína 4 Homóloga a Disks-Large/genética , Proteína 4 Homóloga a Disks-Large/metabolismo , Feminino , Cones de Crescimento/efeitos dos fármacos , Masculino , Camundongos , Camundongos Knockout , Microtúbulos/efeitos dos fármacos , Microtúbulos/patologia , Neurônios/patologia , Gravidez
8.
J Helminthol ; 94: e56, 2019 Jun 28.
Artigo em Inglês | MEDLINE | ID: mdl-31248467

RESUMO

The causes of the beaching and death of sea turtles have not been fully clarified and continue to be studied. Mild, moderate and severe lesions caused by spirorchiidiosis have been seen for decades in different organs and were recently defined as the cause of death of a loggerhead turtle. In the present study, eyes and optic nerves were analysed in green sea turtles with spirorchiidiosis and no other debilitating factors. Injuries to the optic nerve and choroid layer were described in 235 animals (90%) infected with spirorchiids. Turtles with ocular spirorchiidiosis are approximately three times more likely to be cachectic than turtles with spirorchiidiosis without ocular involvement.


Assuntos
Oftalmopatias/veterinária , Olho/parasitologia , Infecções por Trematódeos/veterinária , Tartarugas/parasitologia , Animais , Brasil , Oftalmopatias/parasitologia , Feminino , Nervo Óptico/parasitologia , Nervo Óptico/patologia , Trematódeos/patogenicidade
9.
Ital J Pediatr ; 45(1): 67, 2019 May 31.
Artigo em Inglês | MEDLINE | ID: mdl-31151476

RESUMO

BACKGROUND: X-linked hypophosphatemic rickets (XLH) is the first cause of inherited hypophosphatemia and is caused by mutation in the PHEX gene, resulting in excessive expression of the phosphaturic factor FGF23. Symptoms are mainly related to rickets in children and osteomalacia in adults and cause several complications that can be highly invalidating. Due to its rarity, XLH is poorly known and diagnosis is frequently delayed. Conventional treatment is based on oral phosphate salts supplementation and activated vitamin D analogs, which however, cannot cure the disease in most cases. OBJECTIVE: Due to the low prevalence of XLH, an experts' opinion survey was conducted across Italian centers to collect data on XLH and on its management. METHODS: A questionnaire was developed by a group of experts to collect data on XLH epidemiology, diagnosis and treatment in Italy. RESULTS: Data from 10 Italian centers (nine of which pediatric) on 175 patients, followed between 1998 and 2017, were included in the survey. Most patients were followed since childhood and 63 children became adults during the investigated period. The diagnosis was made before the age of 1 and between 1 and 5 years in 11 and 50% of cases, respectively. Clinically apparent bone deformities were present in 95% of patients. These were ranked moderate/severe in 75% of subjects and caused growth stunting in 67% of patients. Other frequent complications included bone pain (40%), dental abscesses (33%), and dental malpositions (53%). Treatment protocols varied substantially among centers. Nephrocalcinosis was observed in 34% of patients. Tertiary hyperparathyroidism developed in 6% of patients. CONCLUSIONS: XLH remains a severe condition with significant morbidities.


Assuntos
Raquitismo Hipofosfatêmico Familiar/genética , Doenças Genéticas Ligadas ao Cromossomo X , Padrões de Prática Médica/estatística & dados numéricos , Adolescente , Adulto , Criança , Pré-Escolar , Raquitismo Hipofosfatêmico Familiar/diagnóstico , Raquitismo Hipofosfatêmico Familiar/epidemiologia , Raquitismo Hipofosfatêmico Familiar/terapia , Feminino , Fator de Crescimento de Fibroblastos 23 , Doenças Genéticas Ligadas ao Cromossomo X/diagnóstico , Doenças Genéticas Ligadas ao Cromossomo X/epidemiologia , Doenças Genéticas Ligadas ao Cromossomo X/terapia , Humanos , Lactente , Recém-Nascido , Itália/epidemiologia , Masculino , Inquéritos e Questionários
10.
J Comp Pathol ; 168: 30-34, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-31103056

RESUMO

Although relatively uncommon in horses, infections caused by Mycobacterium spp. may affect the gastrointestinal tract. Mycobacterium branderi is a non-tuberculous Mycobacterium (NTM) that causes respiratory infections in man. Non-tuberculous mycobacteria may also affect horses; however, infection by M. branderi has not yet been reported in this species. This report describes the clinical, pathological, microbiological and molecular findings of M. branderi infection in a horse, causing granulomatous mesenteric lymphadenitis. A 17-year-old Thoroughbred stallion had a 3-month history of chronic diarrhoea, cachexia and ventral and cervical oedema. Necropsy examination revealed severe mesenteric lymphadenomegaly, together with mesenteric lymphangiectasia and diffuse small intestinal mucosal thickening. Microscopically, the mesenteric lymph node had diffuse granulomatous inflammatory infiltration, replacing most of the nodal parenchyma, with multiple acid-fast bacilli within the cytoplasm of macrophages. There was also diffuse lymphangiectasia. Fresh samples of mesenteric lymph nodes yielded no bacterial growth; however, nested polymerase chain reaction products obtained from the mesenteric lymph node samples were consistent with M. branderi. This infection should be included as a differential diagnosis in cases of chronic diarrhoea in horses, especially when granulomatous enteritis and lymphadenitis are also observed.


Assuntos
Doenças dos Cavalos/microbiologia , Doenças dos Cavalos/patologia , Linfadenite Mesentérica/veterinária , Infecções por Mycobacterium não Tuberculosas/veterinária , Animais , Granuloma/veterinária , Cavalos , Masculino , Micobactérias não Tuberculosas
11.
J Biomed Mater Res B Appl Biomater ; 106(2): 546-554, 2018 02.
Artigo em Inglês | MEDLINE | ID: mdl-28199046

RESUMO

Magnetic scaffolds have recently attracted significant attention in tissue engineering due to the prospect of improving bone tissue formation by conveying soluble factors such as growth factors, hormones, and polypeptides directly to the site of implantation, as well as to the possibility of improving implant fixation and stability. The objective of this study was to compare bone tissue formation in a preclinical rabbit model of critical femoral defect treated either with a hydroxyapatite (HA)/magnetite (90/10 wt %) or pure HA porous scaffolds at 4 and 12 weeks after implantation. The biocompatibility and osteogenic activity of the novel magnetic constructs was assessed with analysis of the amount of newly formed bone tissue and its nanomechanical properties. The osteoconductive properties of the pure HA were confirmed. The HA/magnetite scaffold was able to induce and support bone tissue formation at both experimental time points without adverse tissue reactions. Biomechanically, similar properties were obtained from nanoindentation analysis of bone formed following implantation of magnetic and control scaffolds. The results indicate that the osteoconductive properties of an HA scaffold are maintained following inclusion of a magnetic component. These provide a basis for future studies investigating the potential benefit in tissue engineering of applying magnetic stimuli to enhance bone formation. © 2017 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 106B: 546-554, 2018.


Assuntos
Regeneração Óssea/efeitos dos fármacos , Durapatita/farmacologia , Fêmur/lesões , Fêmur/fisiologia , Ácido Hialurônico/farmacologia , Alicerces Teciduais/química , Animais , Modelos Animais de Doenças , Durapatita/química , Compostos Férricos/química , Compostos Férricos/farmacologia , Ácido Hialurônico/química , Nanopartículas de Magnetita/química , Masculino , Osteogênese/efeitos dos fármacos , Porosidade , Coelhos , Engenharia Tecidual
12.
Int J Biol Macromol ; 109: 212-219, 2018 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-29222016

RESUMO

Colorectal carcinoma is one of the most common cancers in adults. As chemotherapy, the first-choice treatment for colorectal carcinoma, is often infeasible due to acquired tumor resistance and several adverse effects, it is important to discover and explore new molecules with better therapeutic action. Snake venom toxins have shown promising results with high cytotoxicity against tumor cells, but their mechanisms of action remain unclear. Here we examined how BjussuLAAO-II, an L-amino acid oxidase isolated from Bothrops jararacussu snake venom, exerts cytotoxicity towards colorectal adenocarcinoma human cells (Caco-2) and human umbilical vein endothelial cell line (HUVEC). A 24-h treatment with BjussuLAAO-II at 0.25 - 5.00 µg/mL diminished cell viability by decreasing (i) mitochondrial activity, assessed by reduction of 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2H-tetrazolium bromide and resazurin; (ii) the activity of acid phosphatases; and (iii) lysosomal function, assessed by neutral red uptake. BjussuLAAO-II also increased intracellular levels of reactive oxygen species and DNA damage, as assessed by fluorescence and the comet assay, respectively. BjussuLAAO-II altered the expression of cell proliferation-related genes, as determined by RT-qPCR: it elevated the expression of the inflammatory cytokine genes TNF and IL6, and lowered the expression of the apoptotic-related genes BAX, BCL2, and RELA. Therefore, BjussuLAAO-II induces Caco-2 cells death by acting on multiple intracellular targets, providing important data for further studies to assess whether these effects are seen in both tumor and normal cells, with the aim of selecting this drug for possible therapeutic purposes in the future.


Assuntos
Proteínas Reguladoras de Apoptose/genética , Citocinas/genética , Dano ao DNA/efeitos dos fármacos , Regulação da Expressão Gênica/efeitos dos fármacos , Mediadores da Inflamação , Estresse Oxidativo/efeitos dos fármacos , Venenos de Serpentes/química , Venenos de Serpentes/farmacologia , Apoptose/genética , Linhagem Celular Tumoral , Células Endoteliais/efeitos dos fármacos , Células Endoteliais/metabolismo , Humanos , Interleucina-6/genética , Proteínas Proto-Oncogênicas c-bcl-2/genética , Espécies Reativas de Oxigênio/metabolismo , Fator de Transcrição RelA/genética , Fatores de Necrose Tumoral/genética , Proteína X Associada a bcl-2/genética
14.
J Parasitol ; 103(6): 801-803, 2017 12.
Artigo em Inglês | MEDLINE | ID: mdl-28737483

RESUMO

Spirorchiids (family Spirorchiidae Stunkard 1921) are a group of flukes that inhabit the circulatory system of turtles. Infection by members of the family Spirorchiidae involves egg deposition in the host bloodstream and accumulation in tissues, which cause inflammatory reactions and embolisms, leading or contributing to the death of the host. Reports of spirorchiid egg lesions in loggerhead turtles ( Caretta caretta Linnaeus, 1758) have only been reported from U.S. hosts. In the present report a female loggerhead sea turtle was found dead on the beach in the north part of the State of Rio de Janeiro, Brazil. During gross necropsy, no parasite egg nodule was found. But the microscopic analysis revealed a mild granulomatous inflammatory process due to eggs from the family Spirorchiidae and both Langhans giant cells and foreign-body giant cells in the heart, kidneys, intestines, lungs, and spleen. The present note is the first record of tissue lesions due to spirorchiid eggs in a loggerhead sea turtle outside the United States.


Assuntos
Trematódeos/fisiologia , Infecções por Trematódeos/veterinária , Tartarugas/parasitologia , Animais , Brasil , Feminino , Histiocitose de Células de Langerhans/parasitologia , Histiocitose de Células de Langerhans/veterinária , Óvulo , Baço/parasitologia , Trematódeos/isolamento & purificação , Infecções por Trematódeos/parasitologia , Infecções por Trematódeos/patologia
15.
J Mech Behav Biomed Mater ; 72: 200-208, 2017 08.
Artigo em Inglês | MEDLINE | ID: mdl-28500999

RESUMO

In joint arthroplasty one of the main issues related to the failure of prosthetic implants is due to the wear of the ultra-high molecular weight polyethylene (UHMWPE) component. Surface treatments and coatings have been recognized as enhancing methods, able to improve the tribological properties of the implants. Therefore, the main objective of this work was to investigate the possibility to fabricate yttria-stabilized zirconia (YSZ) coatings on a metal (AISI 316-L) substrate by means of Pulsed Electron Deposition, in order to improve the tribological behavior of the polymer-metal coupling, by reducing the initial wear of the UHMWPE component. In order to optimize the coating characteristics, the effects of working gas pressure on both its morphological and tribological properties were analyzed. Morphological characterization of the films was evaluated by Atomic Force Microscopy (AFM). Coating wettability was also estimated by contact angle (CA) measurement. Tribological performance (coupling friction and wear of UHMWPE) was evaluated by using a ball-on-disc tribometer during highly-stressing tests in dry and lubricated (i.e. NaCl and serum) conditions; friction and wear were specifically evaluated at the initial sliding distances - to highlight the main effect of coating morphology - and after 100m - where the influence of the intrinsic materials properties prevails. AFM analysis highlighted that the working pressure heavily affected the morphological characteristics of the realized films. The wettability of the coating at the highest and lowest deposition pressures (CA ~ 60°, closed to substrate value) decreased for intermediate pressures, reaching a maximum CA of ~ 90°. Regarding tribological tests, a strong correlation was found in the initial steps between friction coefficient and wettability, which decreased as the distance increased. Concerning UHMWPE wear associated to coated counterpart, at 100m a reduction rate of about 7% in dry, 12% in NaCl and 5% in presence of serum was obtained compared to the uncoated counterpart. Differently from what highlighted for friction, no correlation was found between wear rate and morphological parameters. These findings, in agreement with literature, underlined the effect of the deposition pressure on the morphological properties, but suggested that physical characteristics are influenced too. Further research on the deposition process will be required in order to improve the tribological performance of the coating at long distances, addressing - above all - orthopedic applications.


Assuntos
Teste de Materiais , Próteses e Implantes , Zircônio/análise , Fricção , Humanos , Gases em Plasma , Polietilenos , Pressão , Propriedades de Superfície , Molhabilidade
16.
Clin Genet ; 92(1): 18-25, 2017 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-27460976

RESUMO

DJ-1 mutations are associated to early-onset Parkinson's disease and accounts for about 1-2% of the genetic forms. The protein is involved in many biological processes and its role in mitochondrial regulation is gaining great interest, even if its function in mitochondria is still unclear. We describe a 47-year-old woman affected by a multisystem disorder characterized by progressive, early-onset parkinsonism plus distal spinal amyotrophy, cataracts and sensory-neural deafness associated with a novel homozygous c.461C>A [p.T154K] mutation in DJ-1. Patient's cultured fibroblasts showed low ATP synthesis, high ROS levels and reduced amount of some subunits of mitochondrial complex I; biomarkers of oxidative stress also resulted abnormal in patient's blood. The clinical pattern of multisystem involvement and the biochemical findings in our patient highlight the role for DJ-1 in modulating mitochondrial response against oxidative stress.


Assuntos
Fibroblastos/metabolismo , Estresse Oxidativo/genética , Doença de Parkinson/genética , Proteína Desglicase DJ-1/genética , Trifosfato de Adenosina/biossíntese , Complexo I de Transporte de Elétrons/genética , Complexo I de Transporte de Elétrons/metabolismo , Feminino , Fibroblastos/patologia , Homozigoto , Humanos , Pessoa de Meia-Idade , Mitocôndrias/genética , Mitocôndrias/metabolismo , Mutação , Doença de Parkinson/patologia , Espécies Reativas de Oxigênio/metabolismo
17.
Clin Transl Oncol ; 19(1): 76-83, 2017 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-27041689

RESUMO

INTRODUCTION: SIOPEN INES protocol yielded excellent 5-year survival rates for MYCN-non-amplified metastatic neuroblastoma. Patients deemed ineligible due to lack or delay of MYCN status or late registration were treated, but not included in the study. Our goal was to analyse survival at 10 years among the whole population. MATERIALS AND METHODS: Italian and Spanish metastatic INES patients' data are reported. SPSS 20.0 was used for statistical analysis. RESULTS: Among 98 infants, 27 had events and 19 died, while 79 were disease free. Five- and 10-year event-free survival (EFS) were 73 and 70 %, and overall survival (OS) was 81 and 74 %, respectively. MYCN status was significant for EFS, but not for OS in multivariate analysis. CONCLUSIONS: The survival rates of patients who complied with all the inclusion criteria for INES trials are higher compared to those that included also not registered patients. Five-year EFS and OS for INES 99.2 were 87.8 and 95.7 %, while our stage 4s population obtained 78 and 87 %. Concerning 99.3, 5-year EFS and OS were 86.7 and 95.6 %, while for stage 4 we registered 61 and 68 %. MYCN amplification had a strong impact on prognosis and therefore we consider it unacceptable that many patients were not studied for MYCN and probably inadequately treated. Ten-year survival rates were shown to decrease: EFS from 73 to 70 % and OS from 81 to 74 %, indicating a risk of late events, particularly in stage 4s. Population-based registries like European ENCCA WP 11-task 11 will possibly clarify these data.


Assuntos
Biomarcadores Tumorais/genética , Ensaios Clínicos como Assunto , Amplificação de Genes , Proteína Proto-Oncogênica N-Myc/genética , Neuroblastoma/mortalidade , Criança , Pré-Escolar , Terapia Combinada , Feminino , Seguimentos , Humanos , Lactente , Recém-Nascido , Masculino , Estadiamento de Neoplasias , Neuroblastoma/genética , Neuroblastoma/secundário , Neuroblastoma/terapia , Prognóstico , Taxa de Sobrevida
18.
Toxicology ; 376: 66-74, 2017 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-27181935

RESUMO

The lasiodiplodan (LS) is a ß-(1→6)-d-glucan produced by the fungus Lasiodiplodia theobromae and some of the biological activities of LS were reported as hypoglycemic, anticoagulant, anti-proliferative and anticancer action; however, its effects on DNA instability and modulation of gene expression are still unclear. Aims of study were investigate the genotoxic effects of lasiodiplodan, and its protective activity against DNA damage induced by doxorubicin (DXR) and its impact on the expression of genes associated with DNA damage and inflammatory response pathways. Therefore, Wistar rats were treated (15 days) orally with LS (5.0; 10 and 20mg/kg bw) alone and in combination with DXR (15mg/kg bw; administrated intraperitoneally on 14th day) as well as their respective controls: distilled water and DXR. Monitoring of DNA damage was assessed by comet and micronucleus (MN) assays and gene expression was evaluated by PCR-Arrays. Treatments with LS alone did not induce disturbances on DNA; when LS was given in combination with DXR, comet and MN formations were reduced to those found in the respective controls. Moreover, LS was able to reduce the disturbances on gene expressions induced by DXR treatment, since the animals that receive LS associated with DXR showed no alteration in the expression of genes related to DNA damage response. Also, DXR induced several up- and down-regulation of several genes associated to inflammatory process, while the animals that received LS+DXR had their gene expression patterns similar to those found in the control group. In conclusion, our results showed that LS did not induce disturbances on DNA stability and significantly reduce the DNA damage and inflammation caused by DXR exposure. In addition, we give further information concerning the molecular mechanisms associated to LS protective effects which seems to be a promising nutraceutical with chemopreventive potential.


Assuntos
Análise Citogenética , Dano ao DNA/efeitos dos fármacos , Doxorrubicina/toxicidade , Polissacarídeos Fúngicos/farmacologia , Mediadores da Inflamação/antagonistas & inibidores , Zearalenona/análogos & derivados , Animais , Antibióticos Antineoplásicos/toxicidade , Análise Citogenética/métodos , Dano ao DNA/fisiologia , Relação Dose-Resposta a Droga , Expressão Gênica , Mediadores da Inflamação/metabolismo , Masculino , Substâncias Protetoras/farmacologia , Ratos , Ratos Wistar , Zearalenona/farmacologia
19.
Arq. bras. med. vet. zootec ; 68(5): 1275-1282, set.-out. 2016. tab
Artigo em Inglês | LILACS, VETINDEX | ID: biblio-827883

RESUMO

To conduct the survey were used 35 (thirty-five) red-browned parrots (A. rhodocorytha), adults, captive, of both genders and clinically healthy, belonging to the live collection of the Museum of Biology Teacher Mello Leitao, located in Santa Teresa, Espírito Santo, Brazil. Harvests were performed in the morning, by puncture of the brachial vein getting 0.5mL of blood stored in EDTA for a period no longer than 6 hours. Blood smears of fresh material were made at collection, stained using the method of May-Grunwald-Giemsa. Analysis of blood elements was done by cell counting in a mirrored Neubauer chamber using Natt and Herrick solution at a ratio of 2:200 as diluent. For the analysis of the methodology, homoglobinometry cyanide hemoglobin using commercial kits by colorimetry on a semi-automatic biochemical analyzer was used. After completion of the statistical data the following parameters were obtained (mean±standard deviation): Erythrocytes (x106/µl): 2.68±0.56; Hemoglobin (g/dl): 14.27±0.69; Hematocrit (%): 53±3.38; Mean corpuscular volume (fl): 206.7±45.82; Mean corpuscular hemoglobin (pg): 56.4±14.46; Mean corpuscular hemoglobin concentration (%): 27.5±1.19; Thrombocytes (x3/µl): 25.8 ± 10.5; Total plasma protein (g/dl) 5.4±0.5; Leukocytes (x103/dl): 3.1±2; Heterophile (/uL): 1937±1676; Lymphocytes (/uL): 1144±599; Monocytes (/uL): 24.4 ± 28.2; Basophils (/uL): 42.2±46.2; Eosinophils (/uL): 11.7±19.9. In the relation between males and females, no significant differences were found in any hematological parameter evaluated.(AU)


Para a realização da presente pesquisa, foram utilizados 35 (trinta e cinco) papagaios-chauás (A. rhodocorytha), adultos, cativos, de ambos os sexos e clinicamente saudáveis, pertencentes ao acervo vivo do Museu de Biologia Professor Mello Leitão, localizado em Santa Teresa, Espírito Santo, Brasil. As coletas foram realizadas pela manhã, por meio da punção da veia braquial, obtendo-se 0,5mL de sangue, armazenado em EDTA por um período máximo de seis horas. Foram confeccionados esfregaços sanguíneos de material fresco no momento da coleta, posteriormente corados pelo método May-Grunwald-Giensa. A análise dos elementos sanguíneos foi feita por meio de contagem celular em câmara de Neubauer espelhada, utilizando-se como diluente a solução de Natt e Herrick na proporção de 2:200. Para a análise de hemoglobinometria, foi utilizada a metodologia do cianeto de hemoglobina, utilizando-se kits comerciais por colorimetria em um analisador bioquímico semiautomático. Depois de realizada a estatística dos dados, obtiveram-se os seguintes parâmetros (média±desvio-padrão): hemácias (x106/µL): 2,68±0,56; hemoglobina (g/dL): 14,27±0,69; hematócrito (%): 53±3,38; volume corpuscular médio (fL): 206,7±45,82; hemoglobina corpuscular média (pg): 56,4±14,46; concentração hemoglobina corpuscular média (%): 27,5±1,19; trombócitos (x3/µL): 25,8±10,5; proteína plasmática total (g/dL) 5,4±0,5; leucócitos (x103/dL): 3,1±2; heterófilos (/µL): 1937±1676; linfócitos (/µL): 1144±599; monócitos (/µL): 24,4±28,2; basófilos (/µL): 42,2±46,2; eosinófilos (/µL): 11,7±19,9. Na relação entre machos e fêmeas, não foi encontrada diferença estatística relevante em nenhum parâmetro hematológico avaliado.(AU)


Assuntos
Animais , Amazona/sangue , Contagem de Células Sanguíneas/veterinária , Testes Hematológicos/veterinária , Hemoglobinometria/veterinária , Papagaios/sangue
20.
Seizure ; 40: 59-70, 2016 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-27348062

RESUMO

PURPOSE: Up to one third of epilepsy patients develop pharmacoresistant seizures and many benefit from resective surgery. However, patients with non-lesional focal epilepsy often require intracranial monitoring to localize the seizure focus. Intracranial monitoring carries operative morbidity risk and does not always succeed in localizing the seizures, making the benefit of this approach less certain. We performed a decision analysis comparing three strategies for patients with non-lesional focal epilepsy: (1) intracranial monitoring, (2) vagal nerve stimulator (VNS) implantation and (3) medical management to determine which strategy maximizes the expected quality-adjusted life years (QALYs) for our base cases. METHOD: We constructed two base cases using parameters reported in the medical literature: (1) a young, otherwise healthy patient and (2) an elderly, otherwise healthy patient. We constructed a decision tree comprising strategies for the treatment of non-lesional epilepsy and two clinical outcomes: seizure freedom and no seizure freedom. Sensitivity analyses of probabilities at each branch were guided by data from the medical literature to define decision thresholds across plausible parameter ranges. RESULTS: Intracranial monitoring maximizes the expected QALYs for both base cases. The sensitivity analyses provide estimates of the values of key variables, such as the surgical risk or the chance of localizing the focus, at which intracranial monitoring is no longer favored. CONCLUSION: Intracranial monitoring is favored over VNS and medical management in young and elderly patients over a wide, clinically-relevant range of pertinent model variables such as the chance of localizing the seizure focus and the surgical morbidity rate.


Assuntos
Anticonvulsivantes/uso terapêutico , Técnicas de Apoio para a Decisão , Epilepsia Resistente a Medicamentos/diagnóstico , Epilepsia Resistente a Medicamentos/terapia , Eletrocorticografia/normas , Avaliação de Processos e Resultados em Cuidados de Saúde/estatística & dados numéricos , Estimulação do Nervo Vago/normas , Adulto , Idoso , Eletrocorticografia/efeitos adversos , Eletrocorticografia/estatística & dados numéricos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Anos de Vida Ajustados por Qualidade de Vida , Sensibilidade e Especificidade , Estimulação do Nervo Vago/efeitos adversos , Estimulação do Nervo Vago/estatística & dados numéricos , Adulto Jovem
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