Currently, epidural analgesia is a common procedure for labor analgesia. Although it is considered a safe technique, it is not without complications. Horner's syndrome and paresthesia within the ...trigeminal nerve distribution are rare complications of epidural analgesia. We report a case of a pregnant woman who developed Horner's syndrome and paresthesia within the distribution of the trigeminal nerve following epidural analgesia for the relief of labor pain.
A analgesia peridural é hoje em dia um procedimento comum para analgesia do trabalho de parto. Embora seja considerada uma técnica segura, não está isenta de complicações. A síndrome de Horner e a parestesia do território do nervo trigêmeo são complicações raras da analgesia peridural. Relatamos um caso de uma grávida que desenvolveu a síndrome de Horner e parestesia do território do nervo trigêmeo após analgesia peridural para o alívio da dor do trabalho de parto.
Increased interferon-α (IFN-α) production is a critical component in the pathophysiology of systemic lupus erythematosus (SLE) and other rheumatic autoimmune diseases. Herein, we report the ...characterization of S95021, a fully human IgG1 anti–IFN–α monoclonal antibody (mAb) as a novel therapeutic candidate for targeted patient populations. S95021 was expressed in CHOZN GS−/− cells, purified by chromatography and characterized by using electrophoresis, size exclusion chromatography and liquid chromatography-mass spectrometry. High purity S95021 was obtained as a monomeric entity comprising different charge variants mainly due to N-glycosylation. Surface plasmon resonance kinetics experiments showed strong association rates with all IFN-α subtypes and estimated KDs below picomolar values. Pan–IFN–α-binding properties were confirmed by immunoprecipitation assays and neutralization capacity with reporter HEK-Blue IFN-α/β cells. S95021 was IFN-α-selective and exhibited superior potency and broader neutralization profile when compared with the benchmark anti–IFN–α mAbs rontalizumab and sifalimumab. STAT-1 phosphorylation and the type I IFN gene signature induced in human peripheral blood mononuclear cells by recombinant IFN-α subtypes or plasmas from selected autoimmune patients were efficiently reduced by S95021 in a dose-dependent manner. Together, our results show that S95021 is a new potent, selective and pan IFN-α-neutralizing mAb. It is currently further evaluated as a valid therapeutic candidate in selected autoimmune diseases in which the IFN-α pro-inflammatory pathway is dysregulated.
•Interferon-α (IFN-α) is a key pathogenic player in several autoimmune diseases.•S95021 is a new, natural, fully human, selective and anti-pan IFN-α monoclonal antibody (mAb).•S95021 has high binding affinity to its target, reaching picomolar KD values for all IFN-α subtypes.•S95021 potently inhibits the type I IFN gene signature in immune cells from autoimmune patients.•S95021 is proposed as a promising candidate to treat autoimmune diseases driven by IFN-α.
Over the past decade, comprehensive genomic studies demonstrated that leiomyosarcomas and most of the tumors previously labeled as ‘malignant fibrous histiocytomas' share complex karyotypes and ...genomic profiles, and can be referred to as ‘sarcomas with complex genomics'. We recently reported a series of 160 sarcomas with complex genomics such as leiomyosarcomas, myxofibrosarcomas, pleomorphic liposarcomas/rhabdomyosarcomas and undifferentiated pleomorphic sarcomas. These tumors present with a frequent loss of chromosome 10 region encompassing the tumor suppressor gene PTEN. In the present study, we assessed PTEN genomic level and protein expression in this large series of sarcomas with complex genomics, as well as activation of downstream pathways. PTEN partial genomic loss was observed in only 46% of tumors, especially in well-differentiated leiomyosarcomas, whereas up to 68% of these tumors demonstrate a loss of protein expression on western blot analysis. Specific discrepancies in PTEN immunohistochemical results suggested bias in this latter technique. PTEN mutations were rare, with only 4 point mutations in the 65 samples studied. Subsequent activation of AKT and mTOR pathways was only observed in 2 out of 3 of PTEN-deleted tumors. On the other hand, RICTOR, a major component of the mTOR complex 2, was significantly overexpressed in well-differentiated leiomyosarcomas. These results, confirmed on tissue micro-array immunohistochemical analysis of 459 sarcomas, could suggest a link between RICTOR overexpression and leiomyosarcomas oncogenesis. As therapeutics directed against the mTOR pathway are assessed in sarcomas, RICTOR overexpression in sarcomas and its links to therapeutic response need to be assessed.
Abstract
Systemic sclerosis (SSc) is an autoimmune, inflammatory and fibrotic disease with limited treatment options. Developing new therapies is therefore crucial to address patient needs. To this ...end, we focused on galectin-3 (Gal-3), a lectin known to be associated with several pathological processes seen in SSc. Using RNA sequencing of whole-blood samples in a cross-sectional cohort of 249 patients with SSc, Gal-3 and its interactants defined a strong transcriptomic fingerprint associated with disease severity, pulmonary and cardiac malfunctions, neutrophilia and lymphopenia. We developed new Gal-3 neutralizing monoclonal antibodies (mAb), which were then evaluated in a mouse model of hypochlorous acid (HOCl)-induced SSc. We show that two of these antibodies, D11 and E07, reduced pathological skin thickening, lung and skin collagen deposition, pulmonary macrophage content, and plasma interleukin-5 and -6 levels. Moreover, E07 changed the transcriptional profiles of HOCl-treated mice, resulting in a gene expression pattern that resembled that of control mice. Similarly, pathological pathways engaged in patients with SSc were counteracted by E07 in mice. Collectively, these findings demonstrate the translational potential of Gal-3 blockade as a therapeutic option for SSc.
Ependymomas remain a therapeutic challenge in pediatric neuro-oncology. These tumors are chemoresistant and rather radioresistant and until recently little was known about their biology.
...Histopathological grading of ependymomas according to the WHO classification is neither reproducible, nor correlated with outcome, especially in young children. Characterization of molecular abnormalities in ependymomas offers now a better understanding of their initiation and progression; different biological subtypes of tumors have been described and would need further validation. The identification of new prognostic biomarkers, such as tenascin-C overexpression or chromosome 1q gain, will considerably help patient stratification in future trials. Finally, the recent discovery of specific pathways involved in ependymomas oncogenesis, such as Notch-1or EPHB2 offers new perspectives for the development of targeted therapies.
A comprehensive biological work-out including CGHarray and immunohistochemistry for specific biomarkers should now be recommended for the current management of pediatric ependymoma, especially in young children if radiotherapy has to be omitted in the first line of treatment.
A analgesia peridural é hoje em dia um procedimento comum para analgesia do trabalho de parto. Embora seja considerada uma técnica segura, não está isenta de complicações. A síndrome de Horner e a ...parestesia do território do nervo trigêmeo são complicações raras da analgesia peridural. Relatamos um caso de uma grávida que desenvolveu a síndrome de Horner e parestesia do território do nervo trigêmeo após analgesia peridural para o alívio da dor do trabalho de parto.
Currently, epidural analgesia is a common procedure for labor analgesia. Although it is considered a safe technique, it is not without complications. Horner's syndrome and paresthesia within the trigeminal nerve distribution are rare complications of epidural analgesia. We report a case of a pregnant woman who developed Horner's syndrome and paresthesia within the distribution of the trigeminal nerve following epidural analgesia for the relief of labor pain.
O presente relatório, realizado no âmbito da unidade curricular “Estágio” do Mestrado Integrado em Ciências Farmacêuticas, encontra-se divido em duas partes, a primeira diz respeito à vertente de ...investigação e a segunda ao estágio em Farmácia Comunitária. A primeira parte aborda a temática de “Aplicações de Algas como Ingredientes Cosméticos”. Tendo em conta a atual preferência dos consumidores por ingredientes naturais, a indústria cosmética tem manifestado um forte interesse quer nos extratos de algas quer nos seus metabolitos bioativos. Assim, nos últimos anos, foram realizados inúmeros estudos com o intuito de descobrir e corroborar os benefícios destes ingredientes ao nível da pele. A sua aplicação em produtos cosméticos, no mercado europeu, depende da disponibilidade comercial de ingredientes cosméticos que cumpram os requisitos de qualidade e segurança descritos no Regulamento 1223/2009. Neste relatório são abordados alguns dos desafios do uso de algas em cosméticos, os principais metabolitos responsáveis pelos efeitos das algas ao nível da pele e as suas diversas aplicações no âmbito da cosmética. Ao longo deste trabalho, foram identificados ingredientes cosméticos à base de algas disponíveis no mercado e analisada a documentação disponibilizada pelos fornecedores quanto à sua aplicação, alegações cosméticas e estudos de sustentação realizados. No total foram estudados 21 ingredientes, sendo que no que diz respeito à tipologia de algas usadas verificou-se que 15 são microalgas e as restantes 6 são macroalgas, tendo-se identificado 10 alegações cosméticas. Conclui-se que estão comercialmente disponíveis ingredientes que permitem a formulação de cosméticos à base de algas com aplicações em cuidados de rosto, corporal e capilar. A segunda parte é relativa às atividades desenvolvidas no decorrer do estágio em Farmácia Comunitária, na Figueira da Foz, sob orientação da Dr.ª Paula Alhinho.
Ependymomas are one of the most common pediatric malignant brain tumors. Prognosis, especially in young children, remains poor due to their inherent chemo- and radio-resistance and effective ...treatment remains one of the more difficult tasks in pediatric oncology: up to half of the patients may die from the disease. The only reproducible prognostic factor is the extent of surgery; neither histological grading nor other biomarkers can be used to reliably make treatment decisions in clinical practice. None of the studies identifying new biomarkers have been conducted prospectively, only few have been undertaken within the context of a clinical trial and most have been conducted with limited samples (often including adults and childhood samples). International collaboration is needed to improve ependymoma prognostication.
PDF
