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The spectral distribution is a fundamental property of non-monochromatic optical radiation. It is commonly used in research and practical applications when studying how light interacts with matter and living organisms, including humans. In the field of lighting, mis-conceptions about the spectral distribution of light are responsible for unfounded claims, which pervade the scientific and technical communities. Starting from the definition of the spectral distribution, this paper describes the ambiguities and errors associated with a purely graphical analysis of the spectral distribution. It also emphasizes the importance of considering the particle nature of light in research involving both visual and non-visual effects, which implies using the spectral distribution expressed in the photon system of units, a system that has been seldom used in lighting research for historical reasons. The authors encourage lighting engineers and researchers to determine which system is best suited to their work and then proceed with the correct use of spectral distributions and of spectral weighting functions for applications involving optical radiation.
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OBJECTIVE: To describe the outcome and tolerance in patients treated with anti-TNFα in severe and refractory major vessel disease in Behçet's disease (BD). METHODS: A multicenter study evaluating 18 refractory BD patients with major vessel involvement [pulmonary artery (nâ¯=â¯4), aorta (nâ¯=â¯4) or peripheral artery aneurysm (nâ¯=â¯1) and/or pulmonary artery (nâ¯=â¯7), inferior vena cava (nâ¯=â¯5), or intra-cardiac (nâ¯=â¯3) thrombosis or Budd Chiari Syndrome (nâ¯=â¯2)] treated with anti-TNFα agents. RESULTS: Vascular remission was achieved in 16 (89%) patients. The 9â¯months risk of relapse was significantly higher with conventional immunosuppressants used prior anti-TNFα agents as compared to anti-TNFα therapy [ORâ¯=â¯8.7 (1.42-62.6), pâ¯=â¯0.03]. The median daily dose of corticosteroids significantly decreased at 12â¯months. Side effects included infection (nâ¯=â¯4) and pulmonary edema (nâ¯=â¯1). CONCLUSION: TNFα-antagonists are safe and might be associated with a decreased risk of relapse at 9â¯months compared to conventional immunosuppressants in BD patients with major vessels disease.
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Adalimumab/uso terapêutico , Antirreumáticos/uso terapêutico , Síndrome de Behçet/tratamento farmacológico , Infliximab/uso terapêutico , Trombose/fisiopatologia , Adulto , Doenças da Aorta/etiologia , Doenças da Aorta/fisiopatologia , Síndrome de Behçet/complicações , Síndrome de Behçet/fisiopatologia , Síndrome de Budd-Chiari/etiologia , Síndrome de Budd-Chiari/fisiopatologia , Feminino , Cardiopatias/etiologia , Cardiopatias/fisiopatologia , Humanos , Imunossupressores/uso terapêutico , Infecções , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Artéria Pulmonar/fisiopatologia , Edema Pulmonar , Recidiva , Indução de Remissão , Estudos Retrospectivos , Índice de Gravidade de Doença , Trombose/etiologia , Fator de Necrose Tumoral alfa/antagonistas & inibidores , Doenças Vasculares/etiologia , Doenças Vasculares/fisiopatologia , Veia Cava Inferior/fisiopatologia , Adulto JovemRESUMO
OBJECTIVE: To report the efficacy and safety of anti-TNF agents in patients with severe and/or refractory manifestations of Behçet's disease (BD). METHODS: We performed a multicenter study of main characteristics and outcomes of anti-TNF alpha treatments [mainly infliximab (62%), and adalimumab (30%)] in 124 BD patients [48% of men; median age of 33.5 (28-40) years]. RESULTS: Overall response (i.e. complete and partial) rate was 90.4%. Clinical responses were observed in 96.3%, 88%, 70%, 77.8%, 92.3% and 66.7% of patients with severe and/or refractory ocular, mucocutaneous, joint, gastro-intestinal manifestations, central nervous system manifestations and cardiovascular manifestations, respectively. No significant difference was found with respect to the efficacy of anti-TNF used as monotherapy or in association with an immunosuppressive agent. The incidence of BD flares/patient/year was significantly lower during anti-TNF treatment (0.2 ± 0.5 vs 1.7 ± 2.4 before the use of anti-TNF, p < 0.0001). The prednisone dose was significantly reduced at 6 and 12 months (p < 0.0001). In multivariate analysis, retinal vasculitis was negatively associated with complete response to anti-TNF (OR = 0.33 [0.12-0.89]; p = 0.03). The efficacy and relapse free survival were similar regardless of the type of anti-TNF agent used. After a median follow-up of 21 [7-36] months, side effects were reported in 28% of patients, including infections (16.3%) and hypersensitivity reactions (4.1%). Serious adverse events were reported in 13% of cases. CONCLUSION: Anti-TNF alpha therapy is efficient in all severe and refractory BD manifestations. Efficacy appears to be similar regardless of the anti-TNF agent used (infliximab or adalimumab).
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Anticorpos Monoclonais/uso terapêutico , Síndrome de Behçet/tratamento farmacológico , Fatores Imunológicos/uso terapêutico , Fator de Necrose Tumoral alfa/antagonistas & inibidores , Adulto , Anticorpos Monoclonais/administração & dosagem , Anticorpos Monoclonais/efeitos adversos , Síndrome de Behçet/diagnóstico , Síndrome de Behçet/metabolismo , Síndrome de Behçet/mortalidade , Feminino , Humanos , Fatores Imunológicos/administração & dosagem , Fatores Imunológicos/efeitos adversos , Imunossupressores/administração & dosagem , Imunossupressores/efeitos adversos , Imunossupressores/uso terapêutico , Masculino , Recidiva , Retratamento , Estudos Retrospectivos , Índice de Gravidade de Doença , Resultado do TratamentoRESUMO
PURPOSE: To evaluate whether anti-vascular endothelial growth factor (VEGF) neutralizing antibodies injected in the vitreous of rat eyes influence retinal microglia and macrophage activation. To dissociate the effect of anti-VEGF on microglia and macrophages subsequent to its antiangiogenic effect, we chose a model of acute intraocular inflammation. METHODS: Lewis rats were challenged with systemic lipopolysaccharide (LPS) injection and concomitantly received 5 µl of rat anti-VEGF-neutralizing antibody (1.5 mg/ml) in the vitreous. Rat immunoglobulin G (IgG) isotype was used as the control. The effect of anti-VEGF was evaluated at 24 and 48 h clinically (uveitis scores), biologically (cytokine multiplex analysis in ocular media), and histologically (inflammatory cell counts on eye sections). Microglia and macrophages were immunodetected with ionized calcium-binding adaptor molecule 1 (IBA1) staining and counted based on their differential shapes (round amoeboid or ramified dendritiform) on sections and flatmounted retinas using confocal imaging and automatic quantification. Activation of microglia was also evaluated with inducible nitric oxide synthase (iNOS) and IBA1 coimmunostaining. Coimmunolocalization of VEGF receptor 1 and 2 (VEGF-R1 and R2) with IBA1 was performed on eye sections with or without anti-VEGF treatment. RESULTS: Neutralizing rat anti-VEGF antibodies significantly decreased ocular VEGF levels but did not decrease the endotoxin-induced uveitis (EIU) clinical score or the number of infiltrating cells and cytokines in ocular media (interleukin [IL]-1ß, IL-6, tumor necrosis factor [TNF]-α, and monocyte chemoattractant protein [MCP]-1). Eyes treated with anti-VEGF showed a significantly decreased number of activated microglia and macrophages in the retina and the choroid and decreased iNOS-positive microglia. IBA1-positive cells expressed VEGF-R1 and R2 in the inflamed retina. CONCLUSIONS: Microglia and macrophages expressed VEGF receptors, and intravitreous anti-VEGF influenced the microglia and macrophage activation state. Taking into account that anti-VEGF drugs are repeatedly injected in the vitreous of patients with retinal diseases, part of their effects could result from unsuspected modulation of the microglia activation state. This should be further studied in other ocular pathogenic conditions and human pathology.
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Anticorpos Neutralizantes/uso terapêutico , Ativação de Macrófagos/efeitos dos fármacos , Microglia/patologia , Retina/patologia , Uveíte/tratamento farmacológico , Uveíte/patologia , Fator A de Crescimento do Endotélio Vascular/antagonistas & inibidores , Animais , Anti-Inflamatórios/farmacologia , Anti-Inflamatórios/uso terapêutico , Anticorpos Neutralizantes/farmacologia , Proteínas de Ligação ao Cálcio/metabolismo , Contagem de Células , Modelos Animais de Doenças , Humanos , Lipopolissacarídeos , Proteínas dos Microfilamentos/metabolismo , Microglia/efeitos dos fármacos , Microglia/metabolismo , Testes de Neutralização , Óxido Nítrico Sintase Tipo II/metabolismo , Ratos , Receptores de Fatores de Crescimento do Endotélio Vascular/metabolismo , Retina/efeitos dos fármacos , Retina/enzimologia , Fator A de Crescimento do Endotélio Vascular/metabolismoRESUMO
Inhibition of vascular endothelial growth factor (VEGF) has become the standard of care for patients presenting with wet age-related macular degeneration. However, monthly intravitreal injections are required for optimal efficacy. We have previously shown that electroporation enabled ciliary muscle gene transfer results in sustained protein secretion into the vitreous for up to 9 months. Here, we evaluated the long-term efficacy of ciliary muscle gene transfer of three soluble VEGF receptor-1 (sFlt-1) variants in a rat model of laser-induced choroidal neovascularization (CNV). All three sFlt-1 variants significantly diminished vascular leakage and neovascularization as measured by fluorescein angiography (FA) and flatmount choroid at 3 weeks. FA and infracyanine angiography demonstrated that inhibition of CNV was maintained for up to 6 months after gene transfer of the two shortest sFlt-1 variants. Throughout, clinical efficacy was correlated with sustained VEGF neutralization in the ocular media. Interestingly, treatment with sFlt-1 induced a 50% downregulation of VEGF messenger RNA levels in the retinal pigment epithelium and the choroid. We demonstrate for the first time that non-viral gene transfer can achieve a long-term reduction of VEGF levels and efficacy in the treatment of CNV.
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Neovascularização de Coroide/genética , Neovascularização de Coroide/terapia , Corpo Ciliar/metabolismo , Terapia Genética/métodos , Transfecção/métodos , Fator A de Crescimento do Endotélio Vascular/genética , Receptor 1 de Fatores de Crescimento do Endotélio Vascular/genética , Animais , Linhagem Celular , Corioide/metabolismo , Neovascularização de Coroide/metabolismo , Modelos Animais de Doenças , Eletroporação , Feminino , Angiofluoresceinografia , Regulação da Expressão Gênica , Humanos , Neovascularização Patológica/terapia , Plasmídeos , Ratos , Epitélio Pigmentado da Retina/metabolismo , Fator A de Crescimento do Endotélio Vascular/metabolismo , Receptor 1 de Fatores de Crescimento do Endotélio Vascular/metabolismoRESUMO
PURPOSE: To analyze the changes in vicinal kidney parenchyma after percutaneous RFA. MATERIALS AND METHODS: [corrected] Twenty-four CT-guided RFA procedures were performed on six pigs using 2 cm LeVeen coaxial needles. We studied volume, morphology, cavitation and enhancement of the ablation zones (AZ) before and after the procedure on contrast-injected CT-scans. The kidneys were removed four weeks later and studied in the path lab. RESULTS: All the procedures were successfully completed. Four weeks later, the CT-scans showed AZ that were either clearly circumscribed or with unclear borders, heterogenous areas associating necrosis and infarct tissue and mesenchyma showing a process of apoptosis around the edges. A treatment considered as incomplete on the CT-scan (presenting as an enhancement) was always associated with necrosis on the histology slides, although the necrotic areas behaved in various different ways on the CT-scan after injection of contrast medium: an enhancement of more than 10 HU did not mean that no necrotic tissue was present. CONCLUSION: RFA causes heterogenous tissue changes, associating necrotic and ischemic zones and an apoptotic reaction. The mechanisms of these changes and their therapeutic significance should be studied. CT-scans performed immediately after RFA procedure and one month later are not predictive of the efficacy of the treatment because an enhancement of the AZ does not mean that it is not necrotic. The value of a CT-scan performed one month after the procedure is debatable, because the tissue remodeling that occurs in the kidneys is not definitive at this time-point.
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Ablação por Cateter/métodos , Rim/diagnóstico por imagem , Rim/cirurgia , Tomografia Computadorizada por Raios X , Animais , Meios de Contraste , Rim/irrigação sanguínea , Rim/patologia , Modelos Animais , Radiografia Intervencionista , Sus scrofa , Suínos , Resultado do TratamentoRESUMO
The central serous chorioretinopathy (CSCR) is characterized by serous retinal detachments SRD associated with one or several retinal pigment epithelium detachments/irregularities (PEDs). The choroid is thickened with dilated choroidal veins and choroidal hyperpermeability suggesting an underlying choroidopathy. CSCR belongs to the pachychoroid spectrum. CSCR affects mostly middle-aged men and the main risk factor is the corticosteroid intake. In most cases, the subretinal detachment resolves spontaneously with a good visual prognosis. However, recurrent or chronic form of the disease can lead to irreversible retinal damage and decreased visual acuity. Laser on an extra foveal leak point or half dose/half fluence photodynamic therapy are the first-line treatment options.
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Coriorretinopatia Serosa Central , Descolamento Retiniano , Pessoa de Meia-Idade , Masculino , Humanos , Coriorretinopatia Serosa Central/complicações , Coriorretinopatia Serosa Central/diagnóstico , Coriorretinopatia Serosa Central/epidemiologia , Doença Crônica , Angiofluoresceinografia , Descolamento Retiniano/diagnóstico , Descolamento Retiniano/etiologia , Descolamento Retiniano/terapia , Retina , Tomografia de Coerência Óptica , Estudos RetrospectivosRESUMO
Antiphospholipid syndrome (APS) is a chronic autoimmune disease involving vascular thrombosis and/or obstetric morbidity and persistent antibodies to phospholipids or certain phospholipid-associated proteins. It is a rare condition in adults and even rarer in children. The diagnosis of APS can be facilitated by the use of classification criteria based on a combination of clinical and biological features. APS may be rapidly progressive with multiple, often synchronous thromboses, resulting in life-threatening multiple organ failure. This form is known as "catastrophic antiphospholipid syndrome" (CAPS). It may be primary or associated with systemic lupus erythematosus (associated APS) and in very rare cases with other systemic autoimmune diseases. General practitioners and paediatricians may encounter APS in patients with one or more vascular thromboses. Because APS is so rare and difficult to diagnosis (risk of overdiagnosis) any suspected case should be confirmed rapidly and sometimes urgently by an APS specialist. First-line treatment of thrombotic events in APS includes heparin followed by long-term anticoagulation with a VKA, usually warfarin. Except in the specific case of stroke, anticoagulants should be started as early as possible. Any temporary discontinuation of anticoagulants is associated with a high risk of thrombosis in APS. A reference/competence centre specialised in autoimmune diseases must be urgently consulted for the therapeutic management of CAPS.
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Síndrome Antifosfolipídica , Doenças Autoimunes , Lúpus Eritematoso Sistêmico , Trombose , Gravidez , Feminino , Humanos , Adulto , Criança , Síndrome Antifosfolipídica/complicações , Síndrome Antifosfolipídica/diagnóstico , Síndrome Antifosfolipídica/terapia , Anticorpos Antifosfolipídeos , Anticoagulantes/uso terapêutico , Lúpus Eritematoso Sistêmico/complicações , Trombose/diagnóstico , Trombose/epidemiologia , Trombose/etiologia , Doenças Autoimunes/complicaçõesRESUMO
Glial cell line-derived neurotrophic factor (GDNF) is one of the candidate molecules among neurotrophic factors proposed for a potential treatment of retinitis pigmentosa (RP). It must be administered repeatedly or through sustained releasing systems to exert prolonged neuroprotective effects. In the dystrophic Royal College of Surgeon's (RCS) rat model of RP, we found that endogenous GDNF levels dropped during retinal degeneration time course, opening a therapeutic window for GDNF supplementation. We showed that after a single electrotransfer of 30 µg of GDNF-encoding plasmid in the rat ciliary muscle, GDNF was produced for at least 7 months. Morphometric, electroretinographic and optokinetic analyses highlighted that this continuous release of GDNF delayed photoreceptors (PRs) as well as retinal functions loss until at least 70 days of age in RCS rats. Unexpectedly, increasing the GDNF secretion level accelerated PR degeneration and the loss of electrophysiological responses. This is the first report: (i) demonstrating the efficacy of GDNF delivery through non-viral gene therapy in RP; (ii) establishing the efficacy of intravitreal administration of GDNF in RP associated with a mutation in the retinal pigment epithelium; and (iii) warning against potential toxic effects of GDNF within the eye/retina.
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Eletroporação , Terapia Genética/métodos , Fator Neurotrófico Derivado de Linhagem de Célula Glial/genética , Retinose Pigmentar/terapia , Animais , Fator Neurotrófico Ciliar/metabolismo , Modelos Animais de Doenças , Fator Neurotrófico Derivado de Linhagem de Célula Glial/metabolismo , Células Fotorreceptoras de Vertebrados/fisiologia , Plasmídeos , Ratos , Degeneração Retiniana/terapiaRESUMO
Follicular lymphoma (FL) is an indolent, sometimes, fatal disease characterized by recurrence at progressively shorter intervals and is frequently refractive to therapy. Genome-wide association studies have identified single nucleotide polymorphisms (SNPs) in the human leukocyte antigen (HLA) region on chromosome 6p21.32-33 that are statistically significantly associated with FL risk. Low to medium resolution typing of single or multiple HLA genes has provided an incomplete picture of the total genetic risk imparted by this highly variable region. To gain further insight into the role of HLA alleles in lymphomagenesis and to investigate the independence of validated SNPs and HLA alleles with FL risk, high-resolution HLA typing was conducted using next-generation sequencing in 222 non-Hispanic White FL cases and 220 matched controls from a larger San Francisco Bay Area population-based case-control study of lymphoma. A novel protective association was found between the DPB1*03:01 allele and FL risk [odds ratio (OR) = 0.39, 95% confidence interval (CI) = 0.21-0.68]. Extended haplotypes DRB1*01:01-DQA1*01:01-DQB1*05:01 (OR = 2.01, 95% CI = 1.22-3.38) and DRB1*15-DQA1*01-DQB1*06 (OR = 0.55, 95% CI = 0.36-0.82) also influenced FL risk. Moreover, DRB1*15-DQA1*01-DQB1*06 was highly correlated with an established FL risk locus, rs2647012. These results provide further insight into the critical roles of HLA alleles and SNPs in FL pathogenesis that involve multi-locus effects across the HLA region.
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Alelos , Predisposição Genética para Doença , Antígenos de Histocompatibilidade Classe II/genética , Antígenos de Histocompatibilidade Classe I/genética , Linfoma Folicular/genética , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Haplótipos , Humanos , Masculino , Pessoa de Meia-IdadeRESUMO
This article gives a natural decomposition of the suspension of a generalized moment-angle complex or partial product space which arises as the polyhedral product functor described below. The introduction and application of the smash product moment-angle complex provides a precise identification of the stable homotopy type of the values of the polyhedral product functor. One direct consequence is an analysis of the associated cohomology. For the special case of the complements of certain subspace arrangements, the geometrical decomposition implies the homological decomposition in earlier work of others as described below. Because the splitting is geometric, an analogous homological decomposition for a generalized moment-angle complex applies for any homology theory. Implied, therefore, is a decomposition for the Stanley-Reisner ring of a finite simplicial complex, and natural generalizations.
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Algoritmos , Físico-Química , Modelos Teóricos , Simulação por Computador , MatemáticaRESUMO
Systemic diseases, which are in France mainly monitored in internal medicine, affect multiple organs or tissues. While cutaneous or articular manifestations are the most common, neurological involvement is often associated with severity. Diagnosis of peripheral (e.g, neuropathies) or central (e.g, myelitis) nervous disorders is quite easy through clinical examination and dedicated complementary tests. However, neuropsychological manifestations that affect cognition, including memory, attention, executive functions or reasoning, are difficult to diagnose, sometimes trivialized by practitioners. Their causes are often numerous and interrelated. Nevertheless, these cognitive manifestations are closely related to patients' quality of life, affecting their social life, family dynamics and professional integration but also the treatment adherence. The purpose of this review, focused on the example of systemic lupus erythematosus, is to raise awareness of cognitive dysfunction in systemic diseases including their management from diagnosis to treatments. The final aim is to go further into setting up research groups and care programs for patients with cognitive impairment followed in internal medicine.
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Transtornos Cognitivos , Lúpus Eritematoso Sistêmico , Vasculite Associada ao Lúpus do Sistema Nervoso Central , Cognição , Humanos , Medicina Interna , Lúpus Eritematoso Sistêmico/complicações , Lúpus Eritematoso Sistêmico/diagnóstico , Lúpus Eritematoso Sistêmico/terapia , Testes Neuropsicológicos , Qualidade de VidaRESUMO
Mice were constructed carrying prion protein (PrP) transgenes with individual regions of putative secondary structure deleted. Transgenic mice with amino-terminal regions deleted remained healthy at >400 days of age, whereas those with either of carboxy-terminal alpha-helices deleted spontaneously developed fatal CNS illnesses similar to neuronal storage diseases. Deletion of either C-terminal helix resulted in PrP accumulation within cytoplasmic inclusions in enlarged neurons. Deletion of the penultimate C-terminal helix resulted in proliferation of rough endoplasmic reticulum. Mice with the C-terminal helix deleted were affected with nerve cell loss in the hippocampus and proliferation of smooth endoplasmic reticulum. Whether children with the human counterpart of this malady will be found remains to be determined.
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Doenças Priônicas/genética , Príons/biossíntese , Animais , Doenças Genéticas Inatas , Humanos , Corpos de Inclusão/ultraestrutura , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Transgênicos , Mutação , Doenças Priônicas/patologia , Príons/genética , Estrutura Secundária de Proteína , Deleção de Sequência , Relação Estrutura-AtividadeRESUMO
Variations in prions, which cause different incubation times and deposition patterns of the prion protein isoform called PrP(Sc), are often referred to as 'strains'. We report here a highly sensitive, conformation-dependent immunoassay that discriminates PrP(Sc) molecules among eight different prion strains propagated in Syrian hamsters. This immunoassay quantifies PrP isoforms by simultaneously following antibody binding to the denatured and native forms of a protein. In a plot of the ratio of antibody binding to denatured/native PrP graphed as a function of the concentration of PrP(Sc), each strain occupies a unique position, indicative of a particular PrP(Sc) conformation. This conclusion is supported by a unique pattern of equilibrium unfolding of PrP(Sc) found with each strain. Our findings indicate that each of the eight prion strains has a PrP(Sc) molecule with a unique conformation and, in accordance with earlier results, indicate the biological properties of prion strains are 'enciphered' in the conformation of PrP(Sc) and that the variation in incubation times is related to the relative protease sensitivity of PrP(Sc) in each strain.
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Imunoensaio/métodos , Proteínas PrPSc/química , Animais , Encéfalo/patologia , Química Encefálica , Precipitação Química , Cricetinae , Mesocricetus , Fragmentos de Peptídeos/química , Fragmentos de Peptídeos/imunologia , Ácido Fosfotúngstico , Proteínas PrPSc/classificação , Proteínas PrPSc/imunologia , Doenças Priônicas/diagnóstico , Conformação Proteica , Desnaturação ProteicaRESUMO
Retinal effects of systemically administered drugs are rare due to the hematoretinal barriers that protect the retina from circulating active principles. However, some compounds may have direct or indirect toxic effects on the retina through direct interaction with a specific receptor or due to their accumulation within pigment of uveal cells. In the latter case, toxicity is dose-dependent and may be observed years after cessation of medication, as observed with antimalarial drugs. Anti-infective and anti-inflammatory agents, particularly glucocorticoids, are currently injected peri- or intraocularly. The mechanisms and the exact toxicity of glucocorticoids on the retina remain poorly understood. More recently, anti-VEGF has been specifically developed for the treatment of retinal diseases. However, the long-term blockade of VEGF on normal retinal physiology should be determined taking into account VEGF and VEGF receptors expression in the normal and pathologic retina. Whilst enormous advances are made in the treatment of retinal diseases, basic research is still required to define more accurately the molecular targets of drugs to improve their benefits and reduce their potential side effects.
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Retina/efeitos dos fármacos , Doenças Retinianas/induzido quimicamente , Doenças Retinianas/tratamento farmacológico , Corticosteroides/efeitos adversos , Animais , Anti-Inflamatórios/farmacologia , Barreira Hematorretiniana/fisiologia , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos , Humanos , Fenômenos Fisiológicos Oculares/efeitos dos fármacos , Receptores de Fatores de Crescimento do Endotélio Vascular/antagonistas & inibidores , Fator A de Crescimento do Endotélio Vascular/antagonistas & inibidoresRESUMO
Due to the eye's specific anatomical and physiological conformation, the treatment of eye diseases is a real challenge for pharmaceutical therapy. The presence of efficient protective barriers (i.e., the conjunctival and corneal membranes) and protective mechanisms (i.e., blinking and nasolachrymal drainage) makes this organ particularly impervious to local drug therapy. To overcome these issues, numerous strategies have been envisioned using pharmaceutical technology. Many formulations currently on the market or still under development are emulsions or colloidal systems intended to enhance precorneal residence time and corneal penetration, causing a consequent increase in drug bioavailability after instillation. After a review of some recent developments in the field of cyclosporin A formulations for the eye, a novel micellar formulation of cyclosporine A based on a diblock methoxy-poly(ethylene glycol)-hexysubstituted poly(lactides) (MPEG-hexPLA) is described.
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Segmento Anterior do Olho , Ciclosporina/administração & dosagem , Animais , Química Farmacêutica , Coloides , Ciclosporina/uso terapêutico , Sistemas de Liberação de Medicamentos , Emulsões , Humanos , Micelas , Nanopartículas , Soluções Oftálmicas , Poliésteres , PolietilenoglicóisRESUMO
Intravitreal administration has been widely used since 20 years and has been shown to improve the treatment of diseases of the posterior segment of the eye with infectious origin or in edematous maculopathies. This route of administration allows to achieve high concentration of drug in the vitreous and avoids the problems resulting from systemic administration. However, two basic problems limit the use of intravitreal therapy. Many drugs are rapidly cleared from the vitreous humor; therefore, to reach and to maintain effective therapy repeated injections are necessary. Repeated intravitreal injections increase the risk of endophthalmitis, damage to lens, retinal detachment. Moreover, some drugs provoke a local toxicity at their effective dose inducing side-effects and possible retinal lesions. In this context, the development and the use of new drug delivery systems for intravitreal administration are necessary to treat chronic ocular diseases. Among them, particulate systems such as liposomes have been widely studied. Liposomes are easily injectable and permit to reduce the toxicity and to increase the residence time of several drugs in the eye. They are also able to protect in vivo poorly-stable molecules from degradation such as peptides and nucleic acids. Some promising results have been obtained for the treatment of retinitis induced by cytomegalovirus in human and more recently for the treatment of uveitis in animal. Finally, the fate of liposomes in ocular tissues and fluids after their injection into the vitreous and their elimination routes begin to be more known.
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Portadores de Fármacos , Oftalmopatias/tratamento farmacológico , Lipossomos , Preparações Farmacêuticas/administração & dosagem , Corpo Vítreo/fisiologia , Portadores de Fármacos/farmacocinética , Sistemas de Liberação de Medicamentos , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos , Olho/metabolismo , Humanos , Injeções Intravítreas , Lipossomos/farmacocinéticaRESUMO
INTRODUCTION: Neisseria elongata (NE), a Gram-negative, rod-shaped organism, was previously thought to be non-pathogenic. However, in recent years it has become increasingly recognized as a rare cause of infective endocarditis. In this paper, we report a case of NE infective endocarditis and provide a review of the literature. OBJECTIVES: To describe a case of NE endocarditis, and to review the literature in search of any similar cases of this rare condition. CASE REPORT: Our patient is a 77-year-old, otherwise healthy female patient who was found to have mitral valve endocarditis with valve regurgitation. DISCUSSION: NE endocarditis is a rare condition that typically affects the left cardiac chambers and is associated with high risk of embolization. A literature review retrieved 35 other cases. CONCLUSIONS: Our report underlines the rarity of NE endocarditis, insofar as relatively few cases have been reported. The bacterium presents similarities with HACEK organisms and can potentially cause infective endocarditis.
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Endocardite Bacteriana , Endocardite , Doenças das Valvas Cardíacas , Neisseria elongata , Idoso , Endocardite Bacteriana/diagnóstico , Feminino , HumanosRESUMO
CD8 molecules expressed on the surface of a subset of T cells participate in the selection of class I MHC antigen-restricted T cells in the thymus, and in MHC-restricted immune responses of mature class I MHC antigen-restricted T cells. Here we describe an immune-deficient patient with lack of CD8+ peripheral blood cells. The patient presented with Pneumocystis carinii pneumonia and was unable to reject an allogeneic skin graft, but had normal primary and secondary antibody responses. Examination of the patient's thymus revealed that the loss of CD8+ cells occurred during intrathymic differentiation: the patient's immature cortical thymocytes included both CD4+ and CD8+ cells while the mature medullary cells expressed the CD4 but not the CD8 protein on their surface. Northern blot and polymerase chain reaction analyses revealed the presence of CD8 alpha and beta mRNA in the patient's thymus but not in the peripheral blood. Both class I MHC antigen expression and the expressed TCR V beta repertoire are normal in this patient. These data are consistent with an impaired selection of CD8+ cells in the patient's thymus and support the role of the CD8 surface protein in thymic selection previously characterized in genetically manipulated and inbred mice.
Assuntos
Antígenos de Diferenciação de Linfócitos T/imunologia , Síndromes de Imunodeficiência/etiologia , Linfócitos T/imunologia , Timo/imunologia , Antígenos CD8 , Feminino , Antígenos de Histocompatibilidade Classe I/fisiologia , Humanos , Lactente , Receptores de Antígenos de Linfócitos T/genética , Receptores de Antígenos de Linfócitos T/fisiologiaRESUMO
Ocular toxoplasmosis is the principal cause of posterior uveitis and a leading cause of blindness. Animal models are required to improve our understanding of the pathogenesis of this disease. The method currently used for the detection of retinal cysts in animals involves the observation, under a microscope, of all the sections from infected eyes. However, this method is time-consuming and lacks sensitivity. We have developed a rapid, sensitive method for observing retinal cysts in mice infected with Toxoplasma gondii. This method involves combining the flat-mounting of retina - a compromise between macroscopic observation and global analysis of this tissue - and the use of an avirulent recombinant strain of T. gondii expressing the Escherichia coli beta-galactosidase gene, visually detectable at the submacroscopic level. Single cyst unilateral infection was found in six out of 17 mice killed within 28 days of infection, whereas a bilateral infection was found in only one mouse. There was no correlation between brain cysts number and ocular infection.