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1.
Acta Neurochir Suppl ; 135: 361-366, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-38153494

RESUMO

The aim of this study was to determine the relationship between cervical spine sagittal alignment and clinical outcomes after using a standalone intersomatic titanium cage CeSPACE for anterior cervical discectomy and arthrodesis. We present our clinical experience in a group of 180 patients with a mean follow-up for at least 2 years. Patients were evaluated by clinical and radiological assessment preoperatively, immediately after surgery and at regular follow-up. There were 97 male and 83 female patients (average age: 56.6 years) who were preoperatively affected by cervical radiculomyelopathy that was due to spondylosis or cervical disk herniation and who underwent surgical treatment. All patients underwent an anterior discectomy and interbody fusion through the positioning of one or more levels of the CeSPACE device. Compared with the preoperative scores, improvement was seen in postoperative visual analog scale (VAS) scores and Neck Disability Index (NDI) values. The standalone intersomatic titanium cage CeSPACE for anterior cervical discectomy and arthrodesis improved radiculomyelopathy and increased the probability of cervical kyphotic alignment. However, cervical sagittal alignment after surgery was not significantly associated with clinical outcomes in terms of postoperative improvement in VAS scores and NDI values. Similarly, the change in cervical sagittal alignment was not related to visual analog scale scores or Neck Disability Index values.


Assuntos
Espondilose , Titânio , Humanos , Feminino , Masculino , Pessoa de Meia-Idade , Discotomia , Vértebras Cervicais/diagnóstico por imagem , Vértebras Cervicais/cirurgia , Pescoço , Espondilose/diagnóstico por imagem , Espondilose/cirurgia
2.
Int J Oral Maxillofac Surg ; 52(1): 51-59, 2023 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-35934567

RESUMO

The aim of this systematic review and meta-analysis was to assess whether the presence of inferior third molars during sagittal split mandibular ramus osteotomy increases the risk of intraoperative and postoperative complications. The PRISMA protocol was followed in this study, and the review was registered in the PROSPERO database (CRD42020147642). A search was conducted in the MEDLINE (PubMed), Web of Science, Cochrane Central, and Scopus databases on November 1, 2021. Nineteen articles were included, and the variables analysed were unfavourable fractures, infection, neurosensory disturbance, removal of osteosynthesis material, and duration of surgery. Meta-analyses were performed for the variables unfavourable fractures (risk ratio (RR) 0.95, 95% confidence interval (CI) 0.58-1.57, P = 0.84), infection (RR 0.75, 95% CI 0.48-1.18, P = 0.21), and neurosensory disturbance (RR 1.55, 95% CI 0.61-3.91, P = 0.35); no statistically significant difference in the risk of these variables was found between the groups with and without third molars. The third molars did not increase the need to remove fixation material, but increased the surgery time. The presence of the third molar during sagittal split mandibular ramus osteotomy appears not to increase the risk of intraoperative and postoperative complications. The results presented here must be interpreted with caution due to the heterogeneity presented by the observational studies included.


Assuntos
Dente Serotino , Osteotomia Sagital do Ramo Mandibular , Humanos , Osteotomia Sagital do Ramo Mandibular/efeitos adversos , Osteotomia Sagital do Ramo Mandibular/métodos , Dente Serotino/cirurgia , Mandíbula/cirurgia , Complicações Pós-Operatórias/epidemiologia , Duração da Cirurgia
3.
Chemosphere ; 308(Pt 2): 136430, 2022 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-36113654

RESUMO

The use of glyphosate-based herbicides (GBH) has increased dramatically, being currently the most used herbicides worldwide. Glyphosate acts as a chelating agent, capable of chelate metals. The synergistic effects of metals and agrochemicals may pose an environmental problem as they have been shown to induce neurological abnormalities and behavioural changes in aquatic species. However, as their ecotoxicity effects are poorly understood, evaluating the impacts of GBH complexed with metals is an ecological priority. The main objective of the study was to evaluate the potentially toxic effects caused by exposure to a GBH (1 µg a.i. mL-1), alone or complexed with metals (Copper, Manganese, and Zinc (100 µg L-1)), at environmentally relevant concentrations, during the early period of zebrafish (Danio rerio) embryo development (96 h post-fertilization), a promising model for in vivo developmental studies. To clarify the mechanisms of toxicity involved, lethal and sublethal development endpoints were assessed. At the end of the exposure, biochemical and cell death parameters were evaluated and, 24 h later, different behavioural responses were assessed. The results showed that metals induced higher levels of toxicity. Copper caused high mortality, low hatching, malformations, and changes in biochemical parameters, such as decreased Catalase (CAT) activity, increased Glutathione Peroxidase (GPx), Glutathione S-Transferase (GST), reduced Glutathione (GSH) and decreased Acetylcholinesterase (AChE) activity, also inducing apoptosis and changes in larval behaviour. Manganese increased the activity of SODs enzymes. Zinc increased mortality, reactive oxygen species (ROS) levels, superoxide dismutase activity (SODs) and caused a decrease in AChE activity. Embryos/larvae exposed to the combination of GBH/Metal also showed teratogenic effects during their development but in smaller proportions than the metal alone. Although more studies are needed, the results suggest that GBH may interfere with the mechanisms of metal toxicity at the biochemical, physiological, and behavioural levels of zebrafish.


Assuntos
Herbicidas , Poluentes Químicos da Água , Acetilcolinesterase/metabolismo , Animais , Antioxidantes/metabolismo , Catalase/metabolismo , Quelantes/metabolismo , Cobre/metabolismo , Embrião não Mamífero , Glutationa/metabolismo , Glutationa Peroxidase/metabolismo , Glutationa Transferase/metabolismo , Glicina/análogos & derivados , Herbicidas/metabolismo , Manganês/metabolismo , Estresse Oxidativo , Espécies Reativas de Oxigênio/metabolismo , Superóxido Dismutase/metabolismo , Poluentes Químicos da Água/metabolismo , Peixe-Zebra/metabolismo , Zinco/metabolismo , Glifosato
4.
An Acad Bras Cienc ; 94(1): e20190410, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35170627

RESUMO

Anacardic acid is naturally found in various parts of the cashew tree (Anacardium occidentale L.) and marketed as calcium anacardate. This product has antibacterial, antifungal and antioxidant activity, and has been used in humans in the treatment and prevention of cardiovascular and cerebrovascular diseases and tumors. In meat and egg production systems, anacardic acid is used as a substitute for growth-promoting antibiotics. The study objective was to evaluate effects of adding calcium anacardate as source of anacardic acid in laying Japanese quail diet on bird performance and eggs quality. A total of 252 Japanese quail with 22 week-old were studied, using a completely randomized design composed of six treatments with six replicates and seven quails per experimental unit. Treatments applied were: diet without growth promoter; diet with 0,1% growth promoter; and four diets without growth promoter and addition of 0.25; 0.50; 0.75 and 1.0% calcium anacardate (CA), respectively. The data were submitted to analysis of variance and treatment means compared with a SNK test (5%). The data from treatments containing CA were submitted to regression analysis. Treatments did not influence feed intake, egg production, egg weight, egg volume, feed conversion ratio and eggs quality parameters. The addition up to 1% of calcium anacardate in laying Japanese quail diet, does not influence their performance and egg quality.


Assuntos
Cálcio , Coturnix , Ácidos Anacárdicos , Ração Animal/análise , Animais , Dieta , Suplementos Nutricionais , Humanos
5.
An Acad Bras Cienc ; 93(suppl 4): e20210406, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34878049

RESUMO

Synthetic antioxidants (e.g.butylhydroxytoluene, BHT) are routinely used for to restrict oxidative processes of meat products, but they are implicated as harmful to the health of humans. Therefore natural alternatives, such as plant antioxidants, have been sought as replacements. Plant antioxidants when added to the diet can be incorporated into meat and reduce the need for the addition of synthetic antioxidants during processing. The objective of this study was to evaluate the effects of ethanol extracts of mango seeds (EEMS) in the diet of pigs on qualitative parameters and total antioxidant capacity of mortadella produced from these animals. Thirty-two pigs with an average 60 days of age were distributed among four treatments: control=no antioxidant; BHT=200ppm BHT; EEMS200=200ppm of EEMS and EEMS400=400ppm of EEMS. At 145 days of age the animals were slaughtered and loin was removed for the preparation of mortadella, which was analyzed during 90 days of storage at 4°C. A higher content of polyphenolic compounds and, total antioxidant capacity in mortadellas processed with meat of animals which consumed the EEMS400 ration after 60 and 90 days of storage was observed. EEMS polyphenolic antioxidants incorporated into pork through the diet results in an increase of total antioxidant capacity in the processed product.


Assuntos
Mangifera , Carne de Porco , Carne Vermelha , Animais , Antioxidantes , Dieta , Etanol , Oxirredução , Extratos Vegetais/farmacologia , Sementes , Suínos
6.
Biochim Biophys Acta Proteins Proteom ; 1869(6): 140623, 2021 06.
Artigo em Inglês | MEDLINE | ID: mdl-33607274

RESUMO

Ovarian cancer (OvCA) is the most lethal neoplasia among gynecologic malignancies and faces high rates of new cases particularly in South America. In special, the High Grade Serous Ovarian Carcinoma (HGSC) presents very poor prognosis with deaths caused mainly by metastasis. Among several mechanisms involved in metastasis, the Epithelial to Mesenchymal Transition (EMT) molecular reprogramming represents a model for latest stages of cancer progression. EMT promotes important cellular changes in cellular adhesion and cell-cell communication, which particularly depends on the paracrine signaling from neighbor cells. Considering the importance of cellular communication during EMT and metastasis, here we analyzed the changes in the secretome of the ovarian cancer cell line Caov-3 induced to EMT by Epidermal Growth Factor (EGF). Using a combination of GEL-LC-MS/MS and stable isotopic metabolic labelling (SILAC), we identified up-regulated candidates during EMT as a starting point to identify relevant proteins for HGSC. Based on public databases, our candidate proteins were validated and prioritized for further analysis. Importantly, several of the protein candidates were associated with cellular vesicles, which are important to the cell-cell communication and metastasis. Furthermore, the association of candidate proteins with gene expression data uncovered a subset of proteins correlated with the mesenchymal subtype of ovarian cancer. Based on this relevant molecular signature for aggressive ovarian cancer, supported by protein and gene expression data, we developed a targeted proteomic method to evaluate individual OvCA clinical samples. The quantitative information obtained for 33 peptides, representative of 18 proteins, was able to segregate HGSC from other tumor types. Our study highlighted the richness of the secretome and EMT to reveal relevant proteins for HGSC, which could be used in further studies and larger patient cohorts as a potential stratification signature for ovarian cancer tumor that could guide clinical conduct for patient treatment.


Assuntos
Biomarcadores Tumorais/metabolismo , Cistadenocarcinoma Seroso/patologia , Fator de Crescimento Epidérmico/farmacologia , Neoplasias Ovarianas/patologia , Proteômica/métodos , Regulação para Cima , Comunicação Celular/efeitos dos fármacos , Linhagem Celular Tumoral , Cromatografia Líquida , Cistadenocarcinoma Seroso/metabolismo , Transição Epitelial-Mesenquimal/efeitos dos fármacos , Feminino , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Humanos , Marcação por Isótopo , Invasividade Neoplásica , Estadiamento de Neoplasias , Neoplasias Ovarianas/metabolismo , Mapas de Interação de Proteínas/efeitos dos fármacos , Espectrometria de Massas em Tandem
7.
Acta Neurochir (Wien) ; 163(2): 423-440, 2021 02.
Artigo em Inglês | MEDLINE | ID: mdl-33354733

RESUMO

BACKGROUND: Due to the lack of high-quality evidence which has hindered the development of evidence-based guidelines, there is a need to provide general guidance on cranioplasty (CP) following traumatic brain injury (TBI), as well as identify areas of ongoing uncertainty via a consensus-based approach. METHODS: The international consensus meeting on post-traumatic CP was held during the International Conference on Recent Advances in Neurotraumatology (ICRAN), in Naples, Italy, in June 2018. This meeting was endorsed by the Neurotrauma Committee of the World Federation of Neurosurgical Societies (WFNS), the NIHR Global Health Research Group on Neurotrauma, and several other neurotrauma organizations. Discussions and voting were organized around 5 pre-specified themes: (1) indications and technique, (2) materials, (3) timing, (4) hydrocephalus, and (5) paediatric CP. RESULTS: The participants discussed published evidence on each topic and proposed consensus statements, which were subject to ratification using anonymous real-time voting. Statements required an agreement threshold of more than 70% for inclusion in the final recommendations. CONCLUSIONS: This document is the first set of practical consensus-based clinical recommendations on post-traumatic CP, focusing on timing, materials, complications, and surgical procedures. Future research directions are also presented.


Assuntos
Lesões Encefálicas Traumáticas/cirurgia , Conferências de Consenso como Assunto , Craniotomia/normas , Procedimentos de Cirurgia Plástica/normas , Humanos , Hidrocefalia/cirurgia , Itália
8.
Br J Oral Maxillofac Surg ; 59(3): 362-367, 2021 04.
Artigo em Inglês | MEDLINE | ID: mdl-33358030

RESUMO

We used finite element analysis to assess stress on the cortical bone and plate fixation system, as well as mandibular resistance after sagittal split ramus osteotomy with different mandibular advancements and rotations of the occlusal plane. Three-dimensional mandibular models were obtained, and 6mm and 12mm advancements were planned associated with linear, clockwise, and counter-clockwise rotation of the angle of the occlusal plane. Each model was then fixed with one or two 2.0mm system plates and secured with four monocortical screws. A total of 12 models were built and subjected to a vertical load in the lower central incisor ranging from 50N to 500N in 50N increments. Results showed that the 12mm advancement was associated with higher stress on the bone and plate surface. Additionally, the models fixed with two plates exhibited lower plate stress than those fixed with a single plate. Counter-clockwise rotation of the angle of the mandibular plane in the 6mm advancement caused more plate stress, which did not occur in the 12mm advancement. This analysis has shown that change in the occlusal plane in large mandibular advancements does not act as an additional stress factor. These findings can help to better understand the tensions on bone and plate surfaces in patients who need large mandibular advancements that are associated with a change in the occlusal plane, and will aid better surgical planning.


Assuntos
Avanço Mandibular , Fenômenos Biomecânicos , Placas Ósseas , Parafusos Ósseos , Oclusão Dentária , Análise de Elementos Finitos , Humanos , Mandíbula/cirurgia , Osteotomia Sagital do Ramo Mandibular
9.
Eur J Clin Pharmacol ; 75(9): 1219-1226, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31154476

RESUMO

PURPOSE: Vancomycin is commonly used for the management of severe infections; however, vancomycin dosing may be challenging in critically ill patients. This observational study aims to describe the population pharmacokinetics of vancomycin in adult patients with sepsis or septic shock. METHODS: A single-centre retrospective review of adult patients with sepsis or septic shock receiving vancomycin with therapeutic drug monitoring was undertaken. Blood samples taken 1 h after the vancomycin infusion cessation and 30 min prior to the next dose were assayed using the Vitros Crea Slide method. Vancomycin concentrations determined on different days were included. A pharmacokinetic model was developed using Pmetrics for R. Monte Carlo dosing simulations were performed using the final model. RESULTS: Vancomycin concentrations were available for 27 adult patients admitted to the intensive care unit with sepsis or septic shock. A one-compartment pharmacokinetic model with inter-occasion variability of clearance and volume of distribution before and after 72 h adequately described the data. Creatinine clearance normalized to body surface area was included as a covariate on vancomycin clearance. The clearance and volume of distribution within 72 h of admission were 7.29 L/h and 54.20 L, respectively. Monte Carlo simulations suggested that for patients with a creatinine clearance of ≥ 80 mL/min/1.73 m2, vancomycin doses of ≥ 2 g every 8 h are required to consistently achieve key therapeutic targets. CONCLUSIONS: Vancomycin doses ≥ 2 g every 8 h in adult patients with sepsis or septic shock with a creatinine clearance ≥ 80 mL/min/1.73 m2 are likely needed to achieve an optimal therapeutic exposure.


Assuntos
Antibacterianos/farmacocinética , Modelos Biológicos , Sepse/metabolismo , Vancomicina/farmacocinética , Adulto , Antibacterianos/administração & dosagem , Antibacterianos/sangue , Creatinina/metabolismo , Monitoramento de Medicamentos , Enterococcus faecalis/efeitos dos fármacos , Enterococcus faecium/efeitos dos fármacos , Feminino , Humanos , Masculino , Testes de Sensibilidade Microbiana , Pessoa de Meia-Idade , Sepse/sangue , Sepse/tratamento farmacológico , Staphylococcus/efeitos dos fármacos , Vancomicina/administração & dosagem , Vancomicina/sangue
10.
An. acad. bras. ciênc ; 89(2): 1221-1230, Apr.-June 2017. tab
Artigo em Inglês | LILACS | ID: biblio-886698

RESUMO

ABSTRACT Two trials were aimed to evaluate beef tallow in diets with and without emulsifier on performance of pigs at growing-finishing phases. In the first trial, 15 barrows (22.03±0.62 kg) were distributed among three treatments: reference diet; test diet 1 (5% beef tallow) and test diet 2 (10% beef tallow). Beef tallow presented average value of 7130.97 kcal ME/kg. For the performance trail, 30 barrows (24.85±1.18 kg) were distributed among five treatments: T1 - diet with soybean oil and 3230 kcal ME /kg; T2 - diet with beef tallow and 3230 kcal ME/kg; T3 - diet with beef tallow and 3080 kcal ME/kg; T4 - diet with beef tallow, 3080 kcal/kg and 0.1% emulsifier; T5 - diet with beef tallow, 2930 kcal ME/kg and 0.1% emulsifier. Feed conversion was worse in animals fed diet with 3080 kcal ME/kg containing beef tallow and with 2930 kcal ME/kg with beef tallow and emulsifier. For economic availability, animals fed diet with beef tallow and 3230 kcal ME/kg and those fed diet with 3080 kcal ME/kg containing beef tallow and emulsifier, did not differ from animals fed diet with soybean oil, which enables the reduction up to 150 kcal ME/kg be compensated by emulsifier addition.


Assuntos
Animais , Suínos/crescimento & desenvolvimento , Emulsificantes/administração & dosagem , Gorduras/administração & dosagem , Dieta Hiperlipídica/veterinária , Ração Animal , Valores de Referência , Fatores de Tempo , Triglicerídeos/sangue , Óleo de Soja/administração & dosagem , Ingestão de Energia , Aumento de Peso , Reprodutibilidade dos Testes , Digestão/fisiologia , Ácidos Graxos/administração & dosagem , Dieta Hiperlipídica/métodos
11.
An. acad. bras. ciênc ; 89(3,supl): 2479-2484, 2017. tab
Artigo em Inglês | LILACS | ID: biblio-886791

RESUMO

ABSTRACT The aim of this study was to evaluate the effect of Syzygium cumini leaves (SCL) in laying hens diets on productive performance, egg quality and lipid oxidation of yolk. A total of 108 Hysex White laying hens were distributed in a completely randomized design with three treatments and six replicates of six birds each. The treatments consisted of SCL inclusion at dietary levels of 0, 5 and 10 g/kg. There was no significant effect of SCL inclusion on feed intake, laying percentage, weight and egg mass, feed conversion ratio, Haugh units, specific gravity, percentage of yolk, albumen and egg shells and shell thickness. However, the inclusion of SCL significantly influenced the yolk color and yolk lipid oxidation measured by TBARS values. Yolk color increased and TBARS values ​​decreased with the inclusion of SCL. The inclusion of SCL in laying hens diets improves pigmentation and lipid stability of yolk.


Assuntos
Animais , Feminino , Oviposição/efeitos dos fármacos , Extratos Vegetais/análise , Galinhas/fisiologia , Folhas de Planta , Suplementos Nutricionais/análise , Ração Animal/análise , Brasil , Syzygium , Dieta , Casca de Ovo , Gema de Ovo , Fenômenos Fisiológicos da Nutrição Animal
12.
Arq. bras. med. vet. zootec ; 66(2): 471-480, Jan.-Apr. 2014. tab
Artigo em Inglês | LILACS | ID: lil-709287

RESUMO

The aim of this study was to investigate the presence of arsenic, lead and cadmium residues in samples of liver, kidney and muscle of poultry and swine during the years from 2002 to 2008. A total of 1978 samples were analyzed: 1031 of poultry and 947 of swine from Brazilian slaughterhouses. The samples were analyzed at the National Agricultural Laboratory using the atomic absorption spectrometry technique. In poultry, the arsenic residues were detected in 53.6% of liver samples, although no results have exceeded the MRL. In kidneys, 39.7% of the samples showed measurable residues and there was no violation of the limits. Regarding lead, there were 5 contaminated liver samples and 24 contaminated kidney samples (1.5 and 3.6% respectively). In muscle tissue there was only one sample with residues...


Objetivou-se investigar a presença de resíduos de arsênico, chumbo e cádmio em amostras de fígado, rins e músculo de aves e suínos, durante os anos de 2002 a 2008. Um total de 1.978 amostras foi analisado: 1031 de aves e 947 de suínos provenientes de matadouros brasileiros. As amostras foram analisadas no Laboratório Nacional Agropecuário (Lanagro), sendo utilizada a técnica de espectrometria de absorção atômica. Em aves, os resíduos de arsênico foram detectados em 53,6% das amostras de fígado, embora sem exceder o LMR. Nos rins, 39,7% das amostras mostraram resíduos mensuráveis e não houve violação dos limites. Em relação ao chumbo, cinco amostras de fígado e 24 de amostras de rins estavam contaminadas (1,5 e 3,6%, respectivamente). No tecido muscular, houve apenas uma amostra com resíduos. Para o cádmio, 3,8% das amostras apresentavam valores abaixo do LMR. Resíduos de cádmio foram encontrados em 110 amostras de rins (16,3% testados), mas apenas uma ultrapassou o limite máximo permitido pela legislação nacional. Em suínos, resíduos de arsênico foram detectados em 15,3% das amostras de fígado, sem exceder o LMR. Nos rins, 14,2% das amostras apresentaram resíduos mensuráveis...


Assuntos
Animais , Arsênio/isolamento & purificação , Aves/metabolismo , Cádmio/isolamento & purificação , Chumbo/isolamento & purificação , Fígado , Rim , Suínos/metabolismo , Limites Permissíveis de Riscos Ocupacionais/análise , Concentração Máxima Permitida , Metais Pesados/análise
13.
Int J Oral Maxillofac Surg ; 43(5): 564-71, 2014 May.
Artigo em Inglês | MEDLINE | ID: mdl-24239141

RESUMO

This study constituted a comparative assessment of the mechanical resistance of square and rectangular 2.0-mm system three-dimensional miniplates as compared to the standard configuration using two straight miniplates. 90 polyurethane replica mandibles were used for the mechanical trials. Groups 1, 2, and 3 simulated complete symphyseal fractures characterized by linear separation of the central incisors; groups 4, 5, and 6 simulated parasymphyseal fractures with an oblique configuration. Groups 1 and 4 represented the standard method with two straight miniplates set parallel to one another. Square miniplates were used in groups 2 and 5, and rectangular miniplates in groups 3 and 6. A universal testing machine set to a velocity of 10mm/min and delivering a vertical linear load to the first left molar was used to test each group. Maximum load values and load values with pre-established dislocation of 5mm were obtained and submitted to statistical analysis using a calculated reliability interval of 95%. The mechanical performances of the devices were similar, except in the case of rectangular plates used in the parasymphyseal fractures. The innovative fixation methods used showed significantly better results in the case of symphyseal fractures.


Assuntos
Placas Ósseas , Fixação Interna de Fraturas/instrumentação , Fraturas Mandibulares/cirurgia , Fenômenos Biomecânicos , Humanos , Modelos Anatômicos , Poliuretanos , Desenho de Prótese , Estresse Mecânico , Titânio
14.
Mol Cell Proteomics ; 11(12): 1898-912, 2012 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-23001822

RESUMO

Lipid rafts are highly ordered membrane domains rich in cholesterol and sphingolipids that provide a scaffold for signal transduction proteins; altered raft structure has also been implicated in cancer progression. We have shown that 25 µm 10-(octyloxy) decyl-2-(trimethylammonium) ethyl phosphate (ODPC), an alkylphospholipid, targets high cholesterol domains in model membranes and induces apoptosis in leukemia cells but spares normal hematopoietic and epithelial cells under the same conditions. We performed a quantitative (SILAC) proteomic screening of ODPC targets in a lipid-raft-enriched fraction of leukemic cells to identify early events prior to the initiation of apoptosis. Six proteins, three with demonstrated palmitoylation sites, were reduced in abundance. One, the linker for activation of T-cell family member 2 (LAT2), is an adaptor protein associated with lipid rafts in its palmitoylated form and is specifically expressed in B lymphocytes and myeloid cells. Interestingly, LAT2 is not expressed in K562, a cell line more resistant to ODPC-induced apoptosis. There was an early loss of LAT2 in the lipid-raft-enriched fraction of NB4 cells within 3 h following treatment with 25 µm ODPC. Subsequent degradation of LAT2 by proteasomes was observed. Twenty-five µm ODPC inhibited AKT activation via myeloid growth factors, and LAT2 knockdown in NB4 cells by shRNA reproduced this effect. LAT2 knockdown in NB4 cells also decreased cell proliferation and increased cell sensitivity to ODPC (7.5×), perifosine (3×), and arsenic trioxide (8.5×). Taken together, these data indicate that LAT2 is an early mediator of the anti-leukemic activity of alkylphospholipids and arsenic trioxide. Thus, LAT2 may be used as a target for the design of drugs for cancer therapy.


Assuntos
Proteínas Adaptadoras de Transdução de Sinal/metabolismo , Apoptose/efeitos dos fármacos , Fosfolipídeos/farmacologia , Proteínas Proto-Oncogênicas c-akt/metabolismo , Transdução de Sinais/efeitos dos fármacos , Proteínas Adaptadoras de Transdução de Sinal/biossíntese , Proteínas Adaptadoras de Transdução de Sinal/genética , Antineoplásicos/metabolismo , Antineoplásicos/farmacologia , Trióxido de Arsênio , Arsenicais/farmacologia , Caspase 3/metabolismo , Linhagem Celular , Proliferação de Células , Colesterol/metabolismo , Ativação Enzimática , Humanos , Leucemia/tratamento farmacológico , Leucemia/metabolismo , Microdomínios da Membrana , Óxidos/farmacologia , Fosfatidilinositol 3-Quinases/efeitos dos fármacos , Fosfolipídeos/metabolismo , Fosforilcolina/análogos & derivados , Fosforilcolina/farmacologia , Estrutura Terciária de Proteína , Proteoma/análise , Interferência de RNA , RNA Interferente Pequeno
15.
Endocrine ; 42(3): 521-5, 2012 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-22706605

RESUMO

Whenever adrenal cancer (ACC) is completely removed we should face the dilemma to treat by means of adjuvant therapy or not. In our opinion, adjuvant mitotane is the preferable approach in most cases because the majority of patients following radical removal of an ACC have an elevated risk of recurrence. A better understanding of factors that influence prognosis and response to treatment will help in stratifying patients according to their probability of benefiting from adjuvant mitotane, with the aim of sparing unnecessary toxicity to patients who are likely unresponsive. However, until significant advancements take place, we have to deal with uncertainty using our best clinical judgement and personal experience in the clinical decision process. In the present paper, we present the current evidence on adjuvant mitotane treatment and describe the management strategies of patients with ACC after complete surgical resection. We acknowledge the limit that most recommendations are based on personal experience rather than solid evidence.


Assuntos
Neoplasias das Glândulas Suprarrenais/tratamento farmacológico , Neoplasias das Glândulas Suprarrenais/cirurgia , Antineoplásicos Hormonais/uso terapêutico , Quimioterapia Adjuvante/métodos , Mitotano/uso terapêutico , Antineoplásicos Hormonais/administração & dosagem , Administração de Caso , Terapia Combinada , Intervalo Livre de Doença , Humanos , Mitotano/administração & dosagem , Prognóstico
16.
Minerva Endocrinol ; 37(1): 9-23, 2012 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-22382612

RESUMO

Adrenocortical carcinoma (ACC) is a rare aggressive endocrine neoplasm characterized by a 5-year survival of less than 50%. Due to the widespread use of imaging techniques in clinics, ACC is increasingly recognized as an incidentally discovered tumor. Mostly characterized by poor prognosis, ACC is often diagnosed at an advanced stage of disease. Early diagnosis is uncommon; when diagnosed, ACCs are usually large and have invaded adjacent organs, even if metastatic spread to distant sites can be absent. Complete surgical resection is the only potentially curative treatment for patients with localized disease; however, due to a recurrence rate of 50-70% after apparent radical surgery, there is a strong rationale for a concomitant systemic treatment. Adrenolytic therapy with mitotane (o,p>-DDD), administered alone or in combination with others antineoplastic agents, is the primary treatment for patients with advanced ACC and is increasingly used also in an adjuvant setting, even if controversy exists on this issue due to the limitations of the available literature. Despite being in use for many years, the rarity of ACC precluded the organization of randomized trials; thus, many areas of uncertainty and controversy remain regarding the role of this old drug in the clinical management of patients with ACC. The purpose of this paper is to review the current evidence on mitotane treatment in patients with advanced disease and in ACC patients after complete surgical resection as adjuvant treatment.


Assuntos
Neoplasias do Córtex Suprarrenal/tratamento farmacológico , Antineoplásicos Hormonais/uso terapêutico , Carcinoma/tratamento farmacológico , Mitotano/uso terapêutico , Subfamília B de Transportador de Cassetes de Ligação de ATP , Membro 1 da Subfamília B de Cassetes de Ligação de ATP/antagonistas & inibidores , Neoplasias do Córtex Suprarrenal/diagnóstico , Neoplasias do Córtex Suprarrenal/epidemiologia , Neoplasias do Córtex Suprarrenal/cirurgia , Insuficiência Adrenal/induzido quimicamente , Adrenalectomia , Antineoplásicos Hormonais/efeitos adversos , Antineoplásicos Hormonais/química , Antineoplásicos Hormonais/farmacocinética , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Biotransformação , Carcinoma/diagnóstico , Carcinoma/epidemiologia , Carcinoma/cirurgia , Quimioterapia Adjuvante , Ensaios Clínicos como Assunto , Diagnóstico Tardio , Resistencia a Medicamentos Antineoplásicos/efeitos dos fármacos , Feminino , Gastroenteropatias/induzido quimicamente , Humanos , Achados Incidentais , Masculino , Mitotano/administração & dosagem , Mitotano/efeitos adversos , Mitotano/química , Mitotano/farmacocinética , Estrutura Molecular , Proteínas de Neoplasias/antagonistas & inibidores , Pró-Fármacos/farmacocinética , Pró-Fármacos/uso terapêutico , Resultado do Tratamento
17.
Transl Med UniSa ; 1: 243-70, 2011 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-23905037

RESUMO

Glioblastoma Multiforme (GBM) is the most common and lethal of human primary central nervous system (CNS) tumors. Due to the tumour's intrinsic clinical and molecular heterogeneity, choice of initial treatment, prediction of survival, stratification of patients, prediction and monitoring of response to therapy, represent some of the greatest challenges in the management of GBM patients. Patients, despite optimal surgery, radiation and chemotherapy, still have a median survival of 14-16 months. A reason for this dismal prognosis is because of the relative inaccuracy of current prognostic markers, so far based on clinical or pathological variables. Molecular markers that effectively predict response to therapy and survival outcomes are limited. Consequently, there is a strong need to develop novel and independent markers of prognosis. Ideal biomarkers for solid tumors would serve one or more important functions. Telomeres, guanine-rich tandem DNA repeats of the chromosomal end, provide chromosomal stability, regulates important cellular processes, and seem to be implicated in human carcinogenesis. Recently, telomeres have been shown either to be associated with clinical markers of disease progression or to be independent markers of cancer prognosis in solid tumours, including GBM. Nevertheless, a corresponding comprehensive discussion of these promising developments in brain tumours has not yet been available in the literature. Therefore, here we reviewed studies focused on the assessment of telomeric length in brain tumours with the aim to emphasized those findings indicating a potential clinical role of telomeres in GBM. With the aim to enhance the awareness of the potential clinical role of telomeres' length information in GBM, using a southern blot analysis, telomeric length in excised tumour samples was analyzed. Moreover, an attempt to correlated telomere length with patients' overall survival, was also performed. The findings here reviewed shows some contradictory results, due to different tissues used as controls, but mainly to cellular and molecular heterogeneity in GBMs that drive molecular mechanisms controlling telomere length, included telomerase and Alternative Lengthening of Telomeres (ALT), through multiple mechanisms. However, overall these studies, including our own, are consistent with the hypothesis that GBMs' telomeres were always shorter when compared with Normal Brain Tissue (NBT), and together with higher telomerase activity seem to be associated with malignancy and poor outcome; while tumours with ALT phenotype have longer telomeres, "less malignant" behaviour and better prognosis. We conclude that, although not entirely consistent in the type of telomere alteration, i.e., attrition vs. elongation, and unclear on the underlying mechanisms, multiple studies in brain tumours have shown that telomere dysfunctions are associated with parameters of clinical outcome in patients with GBMs and therefore will be part of novel risk assessment and prognostic modalities for patients with these still dismal disease.

18.
Int J Oral Maxillofac Surg ; 38(4): 385-7, 2009 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-19243914

RESUMO

A variety of injectable permanent fillers have been used in orofacial tissues for cosmetic purposes. Most of these substances seem to be well tolerated but adverse reactions have been reported. Foreign body granulomas are a rare adverse reaction to injectable permanent fillers. The authors report the unusual case of a 56-year-old woman with a foreign body granuloma located exclusively in the oral cavity that was due to injection of a permanent filler.


Assuntos
Materiais Biocompatíveis/efeitos adversos , Técnicas Cosméticas/efeitos adversos , Migração de Corpo Estranho/complicações , Granuloma de Corpo Estranho/etiologia , Doenças da Boca/etiologia , Polimetil Metacrilato/efeitos adversos , Feminino , Migração de Corpo Estranho/patologia , Granuloma de Corpo Estranho/patologia , Granuloma de Corpo Estranho/cirurgia , Humanos , Hidrogéis/efeitos adversos , Injeções Subcutâneas/efeitos adversos , Pessoa de Meia-Idade , Doenças da Boca/patologia , Doenças da Boca/cirurgia , Rejuvenescimento , Resultado do Tratamento
19.
Rev. bras. anal. clin ; 40(2): 133-135, 2008. tab, graf
Artigo em Português | LILACS | ID: lil-510335

RESUMO

A hipercolesterolemia é um dos principais fatores de risco para doenças cardiovasculares. Avaliamos os níveis de colesterol total em três cidades do Paraná Douradina, Cianorte e Guaíra. Douradina apresenta de um modo geral característica mais voltada para o cotidiano rural. Realidade diferente foi constatada em Cianorte, considerada hoje um pólo industrial. Guaíra é uma região preparada para o turismo e com grande atividade comercial. Foram analisadas amostras de 600 indivíduos, sendo 200 de cada localidade,distribuídos previamente em diferentes faixas etárias e gênero. Em Douradina observaram-se as menores taxas de colesterol (186,9 ± 2,9 mg/dl), seguido por Cianorte (203,1 ± 1,4 mg/dl) e Guaíra (219,7 ± 3,2 mg/dl). Concluiu-se que houve uma variação de colesteroltotal nas diferentes cidades, mostrando que hábitos regionais influenciam nos níveis de colesterol total sérico.


Assuntos
Humanos , Masculino , Feminino , Adulto , Pessoa de Meia-Idade , Colesterol/análise , Doenças Cardiovasculares/prevenção & controle , Hipercolesterolemia/diagnóstico , Estilo de Vida , Fatores de Risco
20.
Suppl Tumori ; 4(3): S195-6, 2005.
Artigo em Italiano | MEDLINE | ID: mdl-16437983

RESUMO

Cutaneous squamous cell carcinoma (SCC) is, in its most frequent presentation, a moderately aggressive neoplastic disease. It can, however, present in a moltitude of clinico-pathological variants, some of which are characterized by a more malignant attitude. It is important to determine which tumors, among the various histophenotypes, are high risk in order to establish the appropriate treatment and follow-up. Histologic subtype has been considered as a possible variable in determining the prognosis of cutaneous SCC. We report our experience with 3 cases of peculiar variants of cutaneous SCC.


Assuntos
Carcinoma de Células Escamosas/genética , Carcinoma de Células Escamosas/patologia , Neoplasias Cutâneas/genética , Neoplasias Cutâneas/patologia , Adulto , Idoso , Carcinoma de Células Escamosas/classificação , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Fenótipo , Neoplasias Cutâneas/classificação
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