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1.
Eur J Case Rep Intern Med ; 10(6): 003905, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37305007

RESUMO

We report a case of a 19-year-old young male presenting with thyrotoxicosis with inappropriately elevated TSH. Magnetic resonance imaging revealed a pituitary adenoma (8.2 × 9.7 mm), TRH stimulation test showed abnormal blunted TSH response, and serum glycoprotein hormone alpha-sub-unit was elevated. He had no family history of thyroid disease and TRß genetic testing excluded resistance to thyroid hormone action. The diagnosis of thyrotropin-secreting pituitary adenoma (TSHoma) was presumed and long-acting somatostatin analogue was promptly initiated. After two months of octreotide treatment, serum TSH and FT3 returned to within normal ranges. Tumour resection by transsphenoidal surgery was performed and, ten days after surgery, clinical hypothyroidism was achieved, despite detectable TSH levels (TSH 1.02 µU/ml[RR 0.27-4.2]). Although the patient remained euthyroid for the following three years, there was a gradual biochemical elevation in the levels of TSH, FT4, and FT3 over time, reaching serum values above the normal limit in the third year after surgery. Imaging did not show neoplasm recurrence at this point. After two years, the patient presented with clinical manifestations of re-onset thyrotoxicosis, with MRI revealing a T2 hypersignal oval area compatible with a pituitary adenoma. Adenectomy was performed. Histopathological and immunohistochemical analyses revealed a pituitary adenoma with transcription factor PIT1 expression and positivity for TSH and PRL. TSHoma treatment may not be always effective in the first therapeutic approach and recurrences are a possibility, making follow-up essential. The present case highlights the heterogeneity of post-treatment cure criteria and their limitations. LEARNING POINTS: Thyrotropin-secreting pituitary adenomas are rare benign tumours. Proper diagnosis can be challenging, requiring TSH autonomous production and differentiation from resistance to thyroid hormone action (RTH).Undetectable TSH levels one week after surgery and/or positive T3 suppression test or no response to TRH stimulation test seem to be the criteria with the best prognostic value post-treatment.Close clinical, biochemical and imaging follow-up is crucial to detect TSHoma recurrence.

2.
Medicine (Baltimore) ; 101(39): e30825, 2022 Sep 30.
Artigo em Inglês | MEDLINE | ID: mdl-36181020

RESUMO

The increase in life expectancy along with technological advances has translated into a higher number of pituitary adenomas (PA) diagnosed from the age of 65. In the elderly, symptoms related to comorbidities might overlap with endocrine dysfunction, in addition to increasing anesthetic and surgical risks. This study aimed to compare baseline clinical and tumor features between patients with PA from different age groups: younger adults (YA), 18 to 64 years, and older adults (OA), ≥65 years. As secondary outcomes, we also intended to assess: clinical characteristics and tumor features in patients undergoing surgical intervention and surgical data and complications in patients undergoing transphenoidal surgery (TSS). This retrospective cohort study included patients diagnosed with PA in adulthood divided into YA and OA groups. The secondary outcomes were evaluated in the subgroups: patients who underwent pituitary surgery and patients specifically submitted to TSS, who had completed postoperative follow-up ≥ 6 months until July/2020. A total of 401 patients were included, 327 (81.5%) in the YA and 74 (18.5%) in the OA group. Hormone-secreting effects were more common in the YA group (P < .001) and mass effects in the OA group (P = .070). The prevalence of hypertension and diabetes was higher in the OA group (P = .002, P = .011). A larger proportion of nonfunctioning (NF) PA and prolactinomas was found in OA (P < .001) and YA (P = .012), respectively. Macroadenomas were more common in the OA group (P < .001). No differences were found in terms of invasiveness. In the secondary outcome analysis, there was a higher prevalence of NF-PA in those who underwent pituitary surgery. The rate of TSS-related complications was similar between the groups for major, minor and endocrine/electrolyte complications. OA-PA clinically differ from the younger: tend to present more frequently with chronic comorbidities and less frequently with hormone-secreting effects, are more often NF and larger in size without a significant increase in invasiveness. The TSS results were reassuring, proving to be equally safe for the elderly.


Assuntos
Adenoma , Neoplasias Hipofisárias , Prolactinoma , Adenoma/epidemiologia , Adenoma/patologia , Adenoma/cirurgia , Adulto , Idoso , Hormônios , Humanos , Neoplasias Hipofisárias/epidemiologia , Neoplasias Hipofisárias/patologia , Neoplasias Hipofisárias/cirurgia , Estudos Retrospectivos , Resultado do Tratamento
3.
Anal Bioanal Chem ; 413(16): 4311-4320, 2021 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-34003328

RESUMO

Biosurfactants have been investigated as potential alternatives for synthetic surfactants in several areas, for example, in environmental and pharmaceutical fields. In that regard, extensive research has been carried out with sophorolipids and rhamnolipids that also present various biological properties with therapeutic significance. These biosurfactants are obtained as complex mixtures of slightly different molecules, and thus when studying these microbial glycolipids, the ability to identify and purify the produced compounds is of extreme importance. This study aimed to develop improved methodologies for the identification, separation, and purification of sophorolipids and rhamnolipids. Therefore, an ultra-high-performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS) method was modified to ensure faster characterization of both sophorolipids and rhamnolipids, enabling the identification and fragmentation pattern description of 10 and 13 congeners, respectively. The separation and purification of these biosurfactants was achieved with novel reversed-phase solid-phase extraction methods guaranteeing the isolation of different glycolipids, including those considered for their significant biological activity (e.g. antimicrobial, anticancer). It was possible to isolate sophorolipids and rhamnolipids with purity of 94% and 99%, respectively. The methods presented herein can be easily implemented and are expected to make purification of these biosurfactants easier, facilitating the study of their individual properties in further works.


Assuntos
Glicolipídeos/análise , Ácidos Oleicos/análise , Tensoativos/análise , Cromatografia Líquida de Alta Pressão , Glicolipídeos/isolamento & purificação , Ácidos Oleicos/isolamento & purificação , Pseudomonas aeruginosa/química , Saccharomycetales/química , Extração em Fase Sólida , Tensoativos/isolamento & purificação , Espectrometria de Massas em Tandem
4.
J Pediatr Endocrinol Metab ; 34(6): 799-803, 2021 Jun 25.
Artigo em Inglês | MEDLINE | ID: mdl-33818042

RESUMO

OBJECTIVES: Pituitary apoplexy is a rare complication of Cushing's disease (CD), especially in the paediatric age and even more rarely it can occur following anterior pituitary stimulation tests. CASE PRESENTATION: We report a case of a 14-year-old girl who was admitted to our Hospital for evaluation of a possible Cushing's syndrome (CS). Her symptoms and initial laboratory tests were suggestive of CD. Magnetic resonance imaging (MRI) revealed a microadenoma of the pituitary gland. As part of her evaluation she was submitted to a corticotropin-releasing hormone (CRH) stimulation test. Two and a half months later the patient was re-evaluated and presented with both clinical improvement of CS, biochemical resolution of hypercortisolism and tumour size reduction in the MRI, also evidencing a haemorrhagic component favouring the diagnosis of pituitary apoplexy after CRH stimulation test. The patient denied any episodes of severe headache, nausea, vomiting or visual changes. CONCLUSIONS: To our knowledge, the authors report the first case of a pituitary apoplexy after a CRH stimulation test in the paediatric age.


Assuntos
Hormônio Liberador da Corticotropina/efeitos adversos , Testes Diagnósticos de Rotina/efeitos adversos , Hipersecreção Hipofisária de ACTH/diagnóstico , Apoplexia Hipofisária/patologia , Adolescente , Hormônio Liberador da Corticotropina/metabolismo , Feminino , Humanos , Hipersecreção Hipofisária de ACTH/metabolismo , Apoplexia Hipofisária/induzido quimicamente , Prognóstico
5.
Artigo em Inglês | MEDLINE | ID: mdl-33865234

RESUMO

SUMMARY: Pituitary metastasis (PM) can be the initial presentation of an otherwise unknown malignancy. As PM has no clinical or radiological pathognomonic features, diagnosis is challenging. The authors describe the case of a symptomatic PM that revealed a primary lung adenocarcinoma. A 62-year-old woman with multiple sclerosis and no history of malignancy, incidentally presented with a diffusely enlarged and homogeneously enhancing pituitary gland associated with stalk enlargement. Clinical and biochemical evaluation revealed anterior hypopituitarism and diabetes insipidus. Hypophysitis was considered the most likely diagnosis. However, rapid visual deterioration and pituitary growth raised the suspicion of metastatic involvement. A search for systemic malignancy was performed, and CT revealed a lung mass, which proved to be a lung adenocarcinoma. Accordingly, the patient was started on immunotherapy. Resection of the pituitary lesion was performed, and histopathology analysis revealed metastatic lung adenocarcinoma. Following surgery, the patient underwent radiotherapy. More than 2 years after PM detection, the patient shows a clinically relevant response to antineoplastic therapy and no evidence of PM recurrence. LEARNING POINTS: Although rare, metastatic involvement of the pituitary gland has been reported with increasing frequency during the last decades. Pituitary metastasis can be the initial presentation of an otherwise unknown malignancy and should be considered in the differential diagnosis of pituitary lesions, irrespective of a history of malignancy. The sudden onset and rapid progression of visual or endocrine dysfunction from a pituitary lesion should strongly raise the suspicion of metastatic disease. MRI features of pituitary metastasis can overlap with those of other pituitary lesions, including hypophysitis; however, rapid pituitary growth is highly suggestive of metastatic disease. Survival after pituitary metastasis detection has improved over time, encouraging individualized interventions directed to metastasis to improve quality of life and increase survival.

6.
Exp Clin Endocrinol Diabetes ; 129(2): 126-130, 2021 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31426111

RESUMO

PURPOSE: To assess the accuracy of bilateral inferior petrosal sinus sampling both in the differential diagnosis of adrenocorticotrophic hormone dependent Cushing's syndrome and predicting the localization on the pituitary. METHODS: The authors evaluated all patients that undergone bilateral inferior petrosal sinus sampling in a tertiary centre, between January 1995 and March 2018. The probable diagnosis of Cushing's disease was made when the basal central/peripheral gradient was>2 and/or>3 after stimulation with corticotrophin releasing hormone. The localization was suggested when the inter-sinus gradient was>1.4. The results obtained were compared with the post operatory results: compatible histology and positive immunohistochemistry to adrenocorticotrophic hormone and/or the presence of criteria of cure. Sensitivity, specificity and predictive positive value were calculated. RESULTS: A total of 49 patients were evaluated (75.5% female; mean age 45.4±16.3 years old). Bilateral inferior petrosal sinus sampling was compatible with Cushing's disease in 27 out of 28 confirmed cases in histology or by criteria of cure, and was compatible with ectopic secretion in the 2 cases confirmed as ectopic secretion of adrenocorticotrophic hormone (sensitivity 96.4%; specificity 100%). The lateralization calculated was concordant with the results after surgery in 17 out of 27 patients with Cushing's disease - predictive positive value of 63%. Magnetic resonance had a higher predictive value to lateralization - 70.0%. CONCLUSIONS: Bilateral inferior petrosal sinus sampling is a safe and reliable procedure to diagnose Cushing's disease, with great sensitivity and specificity. Nevertheless, the capacity of this procedure to lateralize the lesion inside the pituitary is limited.


Assuntos
Amostragem do Seio Petroso , Hipersecreção Hipofisária de ACTH/diagnóstico , Adenoma Hipofisário Secretor de ACT/diagnóstico , Adenoma Hipofisário Secretor de ACT/metabolismo , Adenoma/diagnóstico , Adenoma/metabolismo , Hormônio Adrenocorticotrópico/metabolismo , Adulto , Síndrome de Cushing/diagnóstico , Síndrome de Cushing/metabolismo , Diagnóstico Diferencial , Feminino , Humanos , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Amostragem do Seio Petroso/métodos , Amostragem do Seio Petroso/normas , Hipersecreção Hipofisária de ACTH/metabolismo , Portugal , Valor Preditivo dos Testes , Estudos Retrospectivos , Sensibilidade e Especificidade
7.
Mater Sci Eng C Mater Biol Appl ; 115: 111147, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32600733

RESUMO

The development of biomaterials that mimicking the hydroxyapatite nanoparticles existent in the immature bone tissue is crucial, especially to accelerate the bone remodeling and regeneration. In this work, it was developed for the first time, hydroxyapatite nanoparticles (NPs) incorporating citrate and zinc (cit-Zn-Hap) in their composition towards a one-step hydrothermal procedure. For comparison purposes, hydroxyapatite NPs incorporating only zinc (Zn-Hap) or citrate (cit-Hap), as well as hydroxyapatite without any of these elements (Hap) were synthesised. The physicochemical characterization was carried out reveling that, the presence of zinc on hydroxyapatite (cit-Zn-Hap), reduced the size of nanoparticles, changed the phosphate environment and decreased the surface charge when compared with cit-Hap nanoparticles. The osteogenic potential of cit-Zn-Hap NPs was analysed in human bone marrow-derived stromal cells (BMSCs), in the absence of osteoinductive factors. NPs were internalized by endocytosis appearing trapped in endosomes and lysosomes scattered through the cytoplasm. Exposure to these NPs resulted in a significant induction of ALP activity, extracellular matrix mineralization, and gene expression of early and later osteogenic transcription factors, as well as of osteoblastic markers. The osteoinductive effect might be regulated, at least in part, by the increased signalling through the canonical WNT pathway. Evaluation of the cell behaviour following exposure to Zn-Hap and cit-Hap strongly suggested a synergistic effect of citrate and Zn in cit-Zn-Hap NPs towards the induction of the osteogenic commitment and functionality of BMSCs. These findings will allow the design of new biomimetic hydroxyapatite nanoparticles with great potential for bone regeneration.


Assuntos
Regeneração Óssea/efeitos dos fármacos , Durapatita/farmacologia , Células-Tronco Mesenquimais/efeitos dos fármacos , Osteogênese/efeitos dos fármacos , Células Cultivadas , Citratos/química , Durapatita/química , Regulação da Expressão Gênica/efeitos dos fármacos , Humanos , Células-Tronco Mesenquimais/citologia , Nanotubos , Tamanho da Partícula , Zinco/química
8.
Artigo em Inglês | LILACS | ID: biblio-1058883

RESUMO

ABSTRACT INTRODUCTION: Adolescence is a stage of great social, family and emotional demands, and the literature has related common mental disorder (CMD) with poor living conditions. OBJECTIVE: To investigate the relationship between CMD and socioeconomic status in Brazilian adolescents aged 12 to 17 years. METHOD: This is a cross-sectional study with data from the Study of Cardiovascular Risk in Adolescents (ERICA - Estudo de Riscos Cardiovasculares em Adolescentes). The outcome was CMD and the exposure was socioeconomic status assessed by race/skin color, maternal schooling, resident/room relationship, type of school, existence of maid and bathroom at home, and work activity. For the calculation of prevalence, the survey mode was used and, in the multivariate analysis, logistic regression with p < 5%, as well as the 95% confidence interval. RESULTS: The prevalence of CMD in girls was 23.3%, and in boys, 11.1%. The variables associated with CMD in girls were age between 15 and 17 years (OR = 1.34; 1.17-1.51), studying in private school (OR = 1.13; 1.01-1.27), having a housemaid (OR = 1.15; 1.00-1.34) and, as a protective factor, unpaid work (OR = 0.64; 0.55-0.75). Boys also had a higher chance of CMD in the highest age group (OR = 1.42; 1.18-1.71) and when they had a housemaid (OR = 1.26; 1.02-1.57), whereas unpaid work decreased this chance (OR = 0.79; 0.67-0.95). CONCLUSION: Socioeconomic variables that were associated with CMD were suggestive of higher economic class, whereas unpaid work favored the mental health of adolescents, results contrary to the literature on socioeconomic status and CMD.


RESUMO INTRODUÇÃO: A adolescência é uma fase de grande demanda social, familiar e emocional, e a literatura tem relacionado o transtorno mental comum (TMC) com piores condições de vida. OBJETIVO: Investigar a relação entre TMC e a condição socioeconômica em adolescentes brasileiros de 12 a 17 anos. MÉTODO: Estudo seccional com os dados do Estudo de Riscos Cardiovasculares em Adolescentes (Erica). O desfecho foi o TMC e a exposição foi a condição socioeconômica avaliada por raça/cor, escolaridade materna, relação morador/cômodo, tipo de escola, existência de empregada e banheiro no domicílio e atividade laboral. Para o cálculo das prevalências, foi utilizado o modo survey e, na análise multivariada, a regressão logística com p < 5%, assim como o intervalo de confiança de 95%. RESULTADOS: A prevalência de TMC em meninas foi 23,3% e em meninos, 11,1%. As variáveis associadas ao TMC nas meninas foram ter idade entre 15 e 17 anos (OR = 1,34; 1,17-1,51), estudar em escola privada (OR = 1,13; 1,01-1,27), ter empregada doméstica (OR = 1,15; 1,00-1,34) e, como fator de proteção, o trabalho não remunerado (OR = 0,64; 0,55-0,75). Os meninos também apresentaram maior chance de TMC na faixa etária mais alta (OR = 1,42; 1,18-1,71) e quando tinham empregada (OR = 1,26; 1,02-1,57), enquanto o trabalho não remunerado diminuiu essa chance (OR = 0,79; 0,67-0,95). CONCLUSÃO: As variáveis socioeconômicas que estiveram associadas ao TMC foram sugestivas de classe econômica mais elevada, enquanto o trabalho não remunerado favoreceu a saúde mental dos adolescentes, resultados contrários à literatura sobre condição socioeconômica e TMC.


Assuntos
Humanos , Masculino , Feminino , Criança , Adolescente , Transtornos Mentais/epidemiologia , Fatores Socioeconômicos , Brasil/epidemiologia , Fatores Sexuais , Saúde Mental , Prevalência , Estudos Transversais , Fatores de Risco , Inquéritos Epidemiológicos , Fatores Etários
9.
Mater Sci Eng C Mater Biol Appl ; 101: 15-26, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31029308

RESUMO

3D-printing and additive manufacturing can be powerful techniques to design customized structures and produce synthetic bone grafts with multifunctional effects suitable for bone repair. In our work we aimed the development of novel multifunctionalized 3D printed poly(lactic acid) (PLA) scaffolds with bioinspired surface coatings able to reduce bacterial biofilm formation while favoring human bone marrow-derived mesenchymal stem cells (hMSCs) activity. For that purpose, 3D printing was used to prepare PLA scaffolds that were further multifunctionalized with collagen (Col), minocycline (MH) and bioinspired citrate- hydroxyapatite nanoparticles (cHA). PLA-Col-MH-cHA scaffolds provide a closer structural support approximation to native bone architecture with uniform macroporous, adequate wettability and an excellent compressive strength. The addition of MH resulted in an adequate antibiotic release profile that by being compatible with local drug delivery therapy was translated into antibacterial activities against Staphylococcus aureus, a main pathogen associated to bone-related infections. Subsequently, the hMSCs response to these scaffolds revealed that the incorporation of cHA significantly stimulated the adhesion, proliferation and osteogenesis-related gene expression (RUNX2, OCN and OPN) of hMSCs. Furthermore, the association of a bioinspired material (cHA) with the antibiotic MH resulted in a combined effect of an enhanced osteogenic activity. These findings, together with the antibiofilm activity depicted strengthen the appropriateness of this 3D-printed PLA-Col-MH-cHA scaffold for future use in bone repair. By targeting bone repair while mitigating the typical infections associated to bone implants, our 3D scaffolds deliver an integrated strategy with the combined effects further envisaging an increase in the success rate of bone-implanted devices.


Assuntos
Regeneração Óssea/efeitos dos fármacos , Colágeno/farmacologia , Durapatita/farmacologia , Minociclina/farmacologia , Nanopartículas/química , Poliésteres/farmacologia , Impressão Tridimensional , Engenharia Tecidual/métodos , Adsorção , Antibacterianos/farmacologia , Biofilmes/efeitos dos fármacos , Liberação Controlada de Fármacos , Regulação da Expressão Gênica/efeitos dos fármacos , Humanos , Células-Tronco Mesenquimais/citologia , Células-Tronco Mesenquimais/efeitos dos fármacos , Células-Tronco Mesenquimais/metabolismo , Células-Tronco Mesenquimais/ultraestrutura , Testes de Sensibilidade Microbiana , Osseointegração/efeitos dos fármacos , Osteogênese/efeitos dos fármacos , Osteogênese/genética , Staphylococcus aureus/efeitos dos fármacos , Alicerces Teciduais/química
10.
Bioprocess Biosyst Eng ; 39(12): 1825-1837, 2016 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-27538771

RESUMO

Sophorolipids (SLs) were produced by Starmerella bombicola. The separation and purification of SLs are a complex process, since they are produced as a mixture of compounds with few structural differences. Solvent extraction is commonly used in downstream processing. In this work, an environmental friendly approach was developed for SLs recovery and purification, based on neutral polymeric sorbents, Amberlite XAD16NTM, XAD18TM, and XAD1600NTM. In batch microassays, key parameters of sorption/desorption process (e.g., contact time, temperature, sorbents, and SLs concentrations) were optimized for separation of acidic and lactonic SLs. Sorption equilibrium was reached after 2-3 h, for all the sorbents tested. Among them XAD1600NTM showed a higher sorption capacity (q max 230 mg g-1), a higher removal (≈100 %) of acidic and lactonic SLs [1 and 2.5 % (w/v)], and the best selectivity. Methanol, ethanol, and acetone were suitable for SLs elution. A selective desorption of SLs was attained with acetonitrile aqueous solutions (v/v): (1) 25 % led to 88.3 % of acidic SLs and (2) 55 % followed by methanol solution (100 %) led to 93.2 % of purified lactonic SLs. This achievement was particularly important regarding SLs potential therapeutic applications, since acidic and lactonic SLs show different biologic activities. In fact, acid SLs show higher virucidal and pro-inflammatory cytokine activity, while lactonic SLs show stronger spermicidal and anti-cancer activity.


Assuntos
Antineoplásicos , Meios de Cultura/química , Lipídeos , Saccharomycetales/crescimento & desenvolvimento , Espermicidas , Antineoplásicos/química , Antineoplásicos/isolamento & purificação , Lipídeos/biossíntese , Lipídeos/química , Lipídeos/isolamento & purificação , Espermicidas/química , Espermicidas/isolamento & purificação
11.
J Mol Recognit ; 28(3): 155-65, 2015 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-25647712

RESUMO

Sophorolipids (SLs) are glycolipid biosurfactants, produced as a mixture of several compounds by some nonpathogenic yeast. In the current study, separation of individual SLs from mixtures with further evaluation of their surface properties and biologic activity on MDA-MB-321 breast cancer cell line were investigated. SLs were biosynthesized by Starmerella bombicola in a culture media supplemented with borage oil. A reverse-phase flash chromatography method with an automated system coupled with a prepacked cartridge was used to separate and purify the main SLs. Compositional analysis of SLs was performed by high-performance liquid chromatography with electrospray ionization mass spectrometry and tandem mass spectrometry. The following diacetylated lactonic SLs were isolated and purified: C18:0, C18:1, C18:2, and C18:3. The critical micelle concentration (CMC) and surface tension at CMC (γCMC ) of the purified SLs showed an increase with the number of double bonds. High cytotoxic effect against MDA-MB-231 cells was observed with C18:0 and C18:1 lactonic SLs. The cytotoxic effects of C18:3 lactonic SL on cancerous cells were for the first time studied. This cytotoxic effect was considerably higher than the promoted by acidic SLs; however, it induced a lower effect than the previously mentioned SLs, C18:0 and C18:1. To our knowledge, for the first time, C18:1 lactonic SL, in selected concentrations, proved to be able to inhibit MDA-MB-231 cell migration without compromising cell viability and to increase intracellular reactive oxygen species.


Assuntos
Antineoplásicos/metabolismo , Antineoplásicos/farmacologia , Neoplasias da Mama/tratamento farmacológico , Glicolipídeos/biossíntese , Glicolipídeos/farmacologia , Saccharomycetales/fisiologia , Linhagem Celular Tumoral , Movimento Celular/efeitos dos fármacos , Cromatografia Líquida/métodos , Meios de Cultura/química , Feminino , Humanos , Óleos de Plantas/farmacologia , Espécies Reativas de Oxigênio/metabolismo , Espectrometria de Massas por Ionização por Electrospray , Espectrometria de Massas em Tandem , Ácido gama-Linolênico/farmacologia
12.
Elife ; 3: e04120, 2014 Dec 08.
Artigo em Inglês | MEDLINE | ID: mdl-25486594

RESUMO

The HIV-1 protein Rev controls a critical step in viral replication by mediating the nuclear export of unspliced and singly-spliced viral mRNAs. Multiple Rev subunits assemble on the Rev Response Element (RRE), a structured region present in these RNAs, and direct their export through the Crm1 pathway. Rev-RRE assembly occurs via several Rev oligomerization and RNA-binding steps, but how these steps are coordinated to form an export-competent complex is unclear. Here, we report the first crystal structure of a Rev dimer-RRE complex, revealing a dramatic rearrangement of the Rev-dimer upon RRE binding through re-packing of its hydrophobic protein-protein interface. Rev-RNA recognition relies on sequence-specific contacts at the well-characterized IIB site and local RNA architecture at the second site. The structure supports a model in which the RRE utilizes the inherent plasticity of Rev subunit interfaces to guide the formation of a functional complex.


Assuntos
HIV-1/genética , RNA Viral/genética , Elementos de Resposta , Replicação Viral/genética , Produtos do Gene rev do Vírus da Imunodeficiência Humana/genética , Transporte Ativo do Núcleo Celular , Sítios de Ligação , Linhagem Celular Tumoral , Núcleo Celular/metabolismo , Núcleo Celular/virologia , Cristalografia por Raios X , Citosol/metabolismo , Citosol/virologia , Escherichia coli/genética , Escherichia coli/metabolismo , Regulação da Expressão Gênica , Células HEK293 , HIV-1/metabolismo , Células HeLa , Interações Hospedeiro-Patógeno , Humanos , Carioferinas/genética , Carioferinas/metabolismo , Modelos Moleculares , Ligação Proteica , Splicing de RNA , RNA Viral/química , RNA Viral/metabolismo , Receptores Citoplasmáticos e Nucleares/genética , Receptores Citoplasmáticos e Nucleares/metabolismo , Proteínas Recombinantes/genética , Proteínas Recombinantes/metabolismo , Transdução de Sinais , Linfócitos T/metabolismo , Linfócitos T/virologia , Produtos do Gene rev do Vírus da Imunodeficiência Humana/química , Produtos do Gene rev do Vírus da Imunodeficiência Humana/metabolismo , Proteína Exportina 1
13.
Rev. bras. anestesiol ; Rev. bras. anestesiol;63(2): 223-226, mar.-abr. 2013. ilus
Artigo em Português | LILACS | ID: lil-671566

RESUMO

JUSTIFICATIVA E OBJETIVOS: A ocorrência de hemorragia subaracnoidea (HSA) durante a gravidez é rara, sendo que cerca de metade é devida a malformações arteriovenosas (MAV). Os autores descrevem a abordagem anestésica de uma grávida de 39 semanas proposta para cesárea, com história de HSA por MAV às 22 semanas. RELATO DO CASO: Grávida de 39 semanas, saudável previamente à gravidez, com antecedentes de HSA às 22 semanas de gestação, manifestada por cefaleias, vômitos e tonturas, sem perda de consciência ou outros déficits à admissão no serviço de urgência. A ressonância magnética (RM) revelou MAV frontal esquerda. Após curto internamento para estabilização e diagnóstico, decidiu-se manter a gravidez e o seguimento ambulatorial multidisciplinar por neurocirurgia e obstetrícia em consulta de alto risco. Optou-se por fazer cesárea eletiva às 39 semanas sob anestesia peridural lombar. No intraoperatório ocorreu um episódio de hipotensão rapidamente revertida com fenilefrina. O Índice de Apgar do recém-nascido foi de 10/10. O cateter peridural foi usado para analgesia pós-operatória, também sem intercorrências. CONCLUSÕES: São muito raros os casos publicados de abordagem anestésica de grávidas com MAV sintomáticas. Todas as decisões tomadas pela equipe multidisciplinar, desde optar por continuar a gravidez ao momento ideal para intervir na MAV, passando pelo tipo de anestesia e analgesia, foram ponderadas em função do risco de dano cerebral. Do ponto de vista anestésico, os autores enfatizam a necessidade de estabilidade hemodinâmica.


BACKGROUND AND OBJECTIVES: Subarachnoid hemorrhage (SAH) during pregnancy is a rare event, and about half the cases are due to arteriovenous malformations (AVM). The authors describe the anesthetic approach of a 39 week pregnant patient scheduled for cesarean section, with a history of SAH due to AVM at 22 week gestation. CASE REPORT: 39 week pregnant patient, healthy prior to pregnancy, with a history of SAH at 22 week gestation, manifested by headache, vomiting, and dizziness without loss of consciousness or other deficits on admission to the emergency room. Magnetic resonance imaging (MRI) revealed a left frontal AVM. After a short hospital stay for stabilization and diagnosis, the final medical decision was to maintain the pregnancy and a multidisciplinary follow-up by neurosurgery and high-risk obstetric consultation. An elective cesarean section was performed at 39 weeks under epidural anesthesia. During the intraoperative period, an episode of hypotension rapidly reversed with phenylephrine occurred. The newborn Apgar score was 10/10. An epidural catheter was used for postoperative analgesia, also uneventful. CONCLUSIONS: There are very few published cases of anesthetic approach for pregnant women with symptomatic AVM. All decisions made by the multidisciplinary team, from choosing to continue the pregnancy to the ideal time for AVM intervention and type of anesthesia and analgesia, were weighted according to the risk of brain damage. Regarding the anesthetic procedure, the authors emphasize the need for hemodynamic stability.


JUSTIFICATIVA Y OBJETIVOS: El aparecimiento de la hemorragia subaracnoidea (HSA) durante el embarazo es algo raro, siendo que aproximadamente la mitad se debe a malformaciones arteriovenosas (MAV). Los autores describen el abordaje anestésico de una embarazada de 39 semanas programada para cesárea, con un historial de HSA por MAV a las 22 semanas. RELATO DEL CASO: Embarazada de 39 semanas, sana antes del embarazo, con antecedentes de HSA a las 22 semanas de gestación que se manifestó por medio de cefaleas, vómitos y mareos, sin la pérdida de la consciencia u otros déficits a la hora de su entrada en el servicio de urgencia. La resonancia magnética (RM) arrojó MAV frontal izquierda. Después de un breve período de ingreso para la estabilización y el diagnóstico, se decidió mantener el embarazo y el acompañamiento ambulatorio multidisciplinario por neurocirugía y obstetricia en consulta de alto riesgo. Se optó por realizar la cesárea electiva a las 39 semanas bajo anestesia epidural lumbar. En el intraoperatorio ocurrió un episodio de hipotensión que fue rápidamente revertido con fenilefrina. El Índice de Apgar del recién nacido fue de 10/10. El catéter epidural fue usado para la analgesia postoperatoria, que también cursó sin intercurrencias. CONCLUSIONES: Son muy raros los casos publicados de abordaje anestésico de embarazadas con MAV sintomáticas. Todas las decisiones tomadas por el equipo multidisciplinario, desde optar por continuar con el embarazo, hasta el momento ideal para intervenir la MAV, pasando por el tipo de anestesia y analgesia, fueron sopesadas en función del riesgo de daño cerebral. Desde el punto de vista anestésico, los autores enfatizan la necesidad de estabilidad hemodinámica.


Assuntos
Adulto , Feminino , Humanos , Gravidez , Anestesia Obstétrica/métodos , Malformações Arteriovenosas Intracranianas/complicações , Complicações Cardiovasculares na Gravidez , Hemorragia Subaracnóidea/etiologia
14.
Rev Bras Anestesiol ; 61(2): 225-7, 228-31, 120-3, 2011.
Artigo em Inglês, Português, Espanhol | MEDLINE | ID: mdl-21474030

RESUMO

BACKGROUND AND OBJECTIVES: The occurrence of acute myocardial infarction (AMI) during pregnancy is rare. The authors describe the case of MI in a 31-week pregnant woman and the importance of a multidisciplinary team for its approach. CASE REPORT: Thirty-one week pregnant woman with history of smoking, alcoholism and hypertension was admitted after an episode of syncope. On admission she was conscious and asymptomatic, although hypotensive. The electrocardiogram showed marked ST-segment elevation in D1, aVL, V1-V6. The cardiac enzymes were positive. The transthoracic echocardiogram showed reduction in septal and left ventricular contractility and an ejection fraction of 30%. Angiography revealed proximal occlusion of the left anterior descending artery. After a non-successful balloon angioplasty, a metallic stent was placed. The patient started therapy with beta-blockers, aspirin and clopidogrel. As for the delivery, we chose to perform a cesarean section four weeks after MI. Clopidogrel was suspended seven days before delivery. The preoperative cardiac function was improved by infusion of levosimendan started the day before. Cesarean section occurred under epidural block. The intraoperative period showed no complications, except for mild hypotension easily corrected with phenylephrine. The Apgar score for the newborn was 9/10. CONCLUSIONS: This is one of the few cases of myocardial infarction and angioplasty reported during pregnancy. The authors discuss the decisions taken by the multidisciplinary team consisting of anesthesiologists, obstetricians, neonatologists and cardiologists, particularly with regard to dual antiplatelet therapy, the type of delivery and anesthesia.


Assuntos
Infarto do Miocárdio/terapia , Complicações Cardiovasculares na Gravidez/terapia , Adulto , Feminino , Humanos , Gravidez , Terceiro Trimestre da Gravidez
15.
Rev. bras. anestesiol ; Rev. bras. anestesiol;61(2): 228-231, mar.-abr. 2011. ilus
Artigo em Português | LILACS | ID: lil-582716

RESUMO

JUSTIFICATIVA E OBJETIVOS: A ocorrência de infarto agudo do miocárdio (IAM) durante a gravidez é rara. Os autores descrevem o caso de IAM numa grávida de 31 semanas e a importância da existência de uma equipe multidisciplinar para sua abordagem. RELATO DO CASO: Grávida de 31 semanas, com antecedentes de tabagismo, alcoolismo e hipertensão, internada após um episódio de síncope. Na admissão, encontrava-se consciente e assintomática, embora hipotensa. O eletrocardiograma evidenciou marcada elevação do segmento ST em DI, AVL, V1-V6. Pesquisa de enzimas cardíacas foi positiva. O ecocardiograma transtorácico demonstrou redução da contratilidade ventricular esquerda e septal e uma fração de ejeção de 30 por cento. A angiografia revelou oclusão proximal da artéria descendente anterior. Por insucesso da angioplastia por balão, foi colocado um stent metálico. A paciente iniciou terapêutica com b-bloqueadores, aspirina e clopidogrel. Em relação ao parto, optou-se por realizar cesariana eletiva, quatro semanas após o IAM. Suspendeu-se o clopidogrel sete dias antes do parto. A função cardíaca pré-operatória foi otimizada com infusão de levosimendana iniciada no dia anterior. A cesariana decorreu sob bloqueio peridural. O período intraoperatório decorreu sem complicações, à exceção de moderada hipotensão facilmente corrigida com fenilefrina. O índice de Apgar do recém-nascido foi de 9/10. CONCLUSÕES: Este é um dos poucos casos de infarto agudo do miocárdio e angioplastia descritos durante a gravidez. Os autores discutem as decisões tomadas pela equipe multidisciplinar, constituída por anestesiologistas, obstetras, cardiologistas e neonatologistas, notadamente no que se refere à dupla antiagregação plaquetária, ao tipo de parto e à anestesia.


BACKGROUND AND OBJECTIVES: The occurrence of acute myocardial infarction (AMI) during pregnancy is rare. The authors describe the case of MI in a 31-week pregnant woman and the importance of a multidisciplinary team for its approach. CASE REPORT: Thirty-one week pregnant woman with history of smoking, alcoholism and hypertension was admitted after an episode of syncope. On admission she was conscious and asymptomatic, although hypotensive. The electrocardiogram showed marked ST-segment elevation in D1, aVL, V1-V6. The cardiac enzymes were positive. The transthoracic echocardiogram showed reduction in septal and left ventricular contractility and an ejection fraction of 30 percent. Angiography revealed proximal occlusion of the left anterior descending artery. After a non-successful balloon angioplasty, a metallic stent was placed. The patient started therapy with beta-blockers, aspirin and clopidogrel. As for the delivery, we chose to perform a cesarean section four weeks after MI. Clopidogrel was suspended seven days before delivery. The preoperative cardiac function was improved by infusion of levosimendan started the day before. Cesarean section occurred under epidural block. The intraoperative period showed no complications, except for mild hypotension easily corrected with phenylephrine. The Apgar score for the newborn was 9 / 10. CONCLUSIONS: This is one of the few cases of myocardial infarction and angioplasty reported during pregnancy. The authors discuss the decisions taken by the multidisciplinary team consisting of anesthesiologists, obstetricians, neonatologists and cardiologists, particularly with regard to dual antiplatelet therapy, the type of delivery and anesthesia.


JUSTIFICATIVA Y OBJETIVOS: El aparecimiento del infarto agudo del miocardio (IAM), durante el embarazo es raro. Los autores describen el caso de IAM en una mujer embarazada de 31 semanas y la importancia de la existencia de un equipo multidisciplinario para su abordaje. RELATO DEL CASO: Embarazada de 31 semanas, con antecedentes de tabaquismo, alcoholismo e hipertensión, que fue ingresada después de presentar un episodio de síncope. A su llegada, estaba consciente y asintomática, aunque hipotensa. El electrocardiograma mostró una fuerte elevación del segmento ST en DI, AVL, V1-V6. La enzimología cardíaca fue positiva. El ecocardiograma transtorácico acusó una reducción en la contratilidad ventricular izquierda y septal, y una fracción de eyección del 30 por ciento. La angiografía reveló la oclusión proximal de la arteria descendiente anterior. Ya que la angioplastia por balón no tuvo éxito, se colocó un stent metálico. La paciente inició terapéutica con b-bloqueantes, aspirina y clopidogrel. Con relación al parto, se optó por realizar la cesárea electiva 4 semanas después del IAM. Se suspendió el clopidogrel siete días antes del parto. La función cardíaca preoperatoria se optimizó con infusión de levosimedan iniciada el día anterior. La cesárea transcurrió bajo el bloqueo epidural. El período intraoperatorio transcurrió sin complicaciones, con excepción de una moderada hipotensión fácilmente corregida con fenilefrina. El índice de Apgar del recién nacido fue de 9/10. CONCLUSIONES: Este es uno de los pocos casos de infarto agudo del miocardio y angioplastia descritos durante el embarazo. Los autores discuten las decisiones tomadas por el equipo multidisciplinario, que estaba constituido por anestesiólogos, obstetras, cardiólogos y neonatólogos, en lo que se refiere a la doble antiagregación plaquetaria, al tipo de parto y a la anestesia.


Assuntos
Humanos , Feminino , Gravidez , Adulto , Angioplastia , Infarto Miocárdico de Parede Anterior , Cesárea , Complicações Cardiovasculares na Gravidez/terapia , Infarto do Miocárdio/terapia , Complicações Cardiovasculares na Gravidez/terapia , Terceiro Trimestre da Gravidez
16.
Br J Haematol ; 116(2): 341-5, 2002 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-11841436

RESUMO

Chronic lymphocytic leukaemia (CLL) is a B-cell disorder, which has a median survival of over 10 years from diagnosis for stage A disease. The natural history of stage A disease is generally indolent or only slowly progressive. It is less well known that CLL may undergo spontaneous regression. We report a series of 10 such cases (eight stage A and two stage B) followed at our institutions.


Assuntos
Cromossomos Humanos Par 12 , Leucemia Linfocítica Crônica de Células B/genética , Trissomia , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Remissão Espontânea
17.
Rev. bras. oftalmol ; 59(3): 192-5, mar. 2000. ilus
Artigo em Português | LILACS | ID: lil-279968

RESUMO

Apresentar um novo exame complementar, Tomografia de Coerência Optica(Optical Coherence Tomography -OCT), pelo qual se obtém imagens tomográficas de alta resoluçäo do tecido ocular na avaliaçäo diagnóstica do buraco de mácula.Local: CVR(Centro de Retina e Vítreo - Rio de Janeiro) e IBOL(Instituto Brasileiro de Oftalmologia -Rio de Janeiro)Método: Os autores comentaräo sobre as características do aparelho, assim como seu mecanismo de execuçäo e interpretaçäo dos achados em pacientes com buraco de mácula.Resultados: Foi demonstrado a importância do OCT na avaliaçäo do buraco de mácula e o porquê de já ser consideredo o exame complementar de escolha para o estudo desta patologia.Conclusäo: O OCT é um exame de grande importância no diagnóstico e acompanhamento do buraco de mácula.


Assuntos
Perfurações Retinianas/cirurgia , Perfurações Retinianas , Tomografia Computadorizada por Raios X , Tomografia Computadorizada por Raios X/tendências
18.
Rev. bras. oftalmol ; 57(10): 789-92, out. 1998. ilus
Artigo em Português | LILACS | ID: lil-280164

RESUMO

Objetivo: Descrever e anmalisar os achados tomográficos em olhos com diagnóstico de oclusäo de artéria retiniana antiga. Material e método: Realizamos OCT em 4 olhos com diagnóstico de oclusäo de artéria retiniana antiga, sendo 2 de artéria central da retina (ACR) e 2 de ramo temporal de ACR, e analisamos os achados nos cortes tomográficos. Resultados: Observamos reduçäo acentuada da espessura retiniana nas áreas vasculizadas pelas artérias trombosadas. A espessura foveal encontrava-se dentro dos padröes da normalidade em todos os casos. Conclusöes: O OCT é um exame coadjuvante útil no diagnóstico de oclusäo de artéria retiniana antiga, onde já houvve revascularizaçäo e os índices oftalmológicos de trombose näo säo evidentes


Assuntos
Oclusão da Artéria Retiniana/diagnóstico , Tomografia
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