An anti-interleukin-2 receptor drug attenuates thelper 1 lymphocytes-mediated inflammation in an acute model of endotoxin-induced uveitis

The aim of the present study was to evaluate the anti-inflammatory efficacy of Daclizumab, an anti-interleukin-2 receptor drug, in an experimental uveitis model upon a subcutaneous injection of lipopolysaccharide into Lewis rats, a valuable model for ocular acute inflammatory processes. The integrity of the blood-aqueous barrier was assessed 24 h after endotoxin-induced uveitis by evaluating two parameters: cell count and protein concentration in aqueous humors. The histopathology of all the ocular structures (cornea, lens, sclera, choroid, retina, uvea, and anterior and posterior chambers) was also considered. Enzyme-linked immunosorbent assays of the aqueous humor samples were performed to quantify the levels of the different chemokine and cytokine proteins. Similarly, a biochemical analysis of oxidative stress-related markers was also assessed. The inflammation observed in the anterior chamber of the eyes when Daclizumab was administered with endotoxin was largely prevented since the aqueous humor protein concentration substantially lowered concomitantly with a significant reduction in the uveal and vitreous histopathological grading. Th1 lymphocytes-related cytokines, such as Interleukin-2 and Interferon-c, also significantly reduced with related anti-oxidant systems recovery. Daclizumab treatment in endotoxin-induced uveitis reduced Th1 lymphocytes-related cytokines, such as Interleukin-2 and Interferon gamma, by about 60–70% and presented a preventive role in endotoxin-induced oxidative stress. This antioxidant protective effect of Daclizumab may be related to several of the observed Daclizumab effects in our study, including IL-6 cytokine regulatory properties and a substantial concomitant drop in INFc. Concurrently, Daclizumab treatment triggered a significant reduction in both the uveal histopathological grading and protein concentration in aqueous humors, but not in cellular infiltration

CNNs for automatic glaucoma assessment using fundus images: an extensive validation

Background Most current algorithms for automatic glaucoma assessment using fundus images rely on handcrafted features based on segmentation, which are affected by the performance of the chosen segmentation method and the extracted features. Among other characteristics, convolutional neural networks (CNNs) are known because of their ability to learn highly discriminative features from raw pixel intensities. Methods In this paper, we employed five different ImageNet-trained models (VGG16, VGG19, InceptionV3, ResNet50 and Xception) for automatic glaucoma assessment using fundus images. Results from an extensive validation using cross-validation and cross-testing strategies were compared with previous works in the literature. Results Using five public databases (1707 images), an average AUC of 0.9605 with a 95% confidence interval of 95.92–97.07%, an average specificity of 0.8580 and an average sensitivity of 0.9346 were obtained after using the Xception architecture, significantly improving the performance of other state-of-the-art works. Moreover, a new clinical database, ACRIMA, has been made publicly available, containing 705 labelled images. It is composed of 396 glaucomatous images and 309 normal images, which means, the largest public database for glaucoma diagnosis. The high specificity and sensitivity obtained from the proposed approach are supported by an extensive validation using not only the cross-validation strategy but also the cross-testing validation on, to the best of the authors’ knowledge, all publicly available glaucoma-labelled databases. Conclusions These results suggest that using ImageNet-trained models is a robust alternative for automatic glaucoma screening system. All images, CNN weights and software used to fine-tune and test the five CNNs are publicly available, which could be used as a testbed for further comparisons

Lipoic acid lessens Th1-mediated inflammation in lipopolysaccharide-induced uveitis reducing selectively Th1 lymphocytes-related cytokines release

Infl ammation results in the production of free radicals. We evaluated the anti-infl ammatory and antioxidant capacity of lipoic acid in an experimental uveitis model upon a subcutaneous injection of endotoxin into Lewis rats. The role of oxidative stress in the endotoxin-induced uveitis model is well-known. Besides, the Th1 response classically performs a central part in the immunopathological process of experimental autoimmune uveitis. Exogenous sources of lipoic acid have been shown to exhibit antioxidant and anti-infl ammatory properties. Our results show that lipoic acid treatment plays a preventive role in endotoxin-induced oxidative stress at 24 h post-administration and reduced Th1 lymphocytes-related cytokines by approximately 50 – 60%. Simultaneously, lipoic acid treatment caused a signifi cant reduction in uveal histopathological grading and in the protein concentration in aqueous humors, but not in cellular infi ltration

The Journal of Physiology

Dendritic spines are the main receptacles of excitatory information in the brain. Their particular morphology, with a small head connected to the dendrite by a slender neck, has inspired theoretical and experimental work to understand how these structural features affect the processing, storage and integration of synaptic inputs in pyramidal neurons (PNs). The activation of glutamate receptors in spines triggers a large voltage change as well as calcium signals at the spine head. Thus, voltage-gated and calcium-activated potassium channels located in the spine head likely play a key role in synaptic transmission. Here we study the presence and function of large conductance calcium-activated potassium (BK) channels in spines from layer 5 PNs. We found that BK channels are localized to dendrites and spines regardless of their size, but their activity can only be detected in spines with small head volumes (≤0.09 μm3), which reduces the amplitude of two-photon uncaging excitatory postsynaptic potentials recorded at the soma. In addition, we found that calcium signals in spines with small head volumes are significantly larger than those observed in spines with larger head volumes. In accordance with our experimental data, numerical simulations predict that synaptic inputs impinging onto spines with small head volumes generate voltage responses and calcium signals within the spine head itself that are significantly larger than those observed in spines with larger head volumes, which are sufficient to activate spine BK channels. These results show that BK channels are selectively activated in small-headed spines, suggesting a new level of dendritic spine-mediated regulation of synaptic processing, integration and plasticity in cortical PNs. Key points BK channels are expressed in the visual cortex and layer 5 pyramidal neuron somata, dendrites and spines regardless of their size. BK channels are selectively activated in small-headed spines (≤0.09 μm3), which reduces the amplitude of two-photon (2P) uncaging excitatory postsynaptic potentials (EPSPs) recorded at the soma. Two-photon imaging revealed that intracellular calcium responses in the head of 2P-activated spines are significantly larger in small-headed spines (≤0.09 μm3) than in spines with larger head volumes. In accordance with our experimental data, numerical simulations showed that synaptic inputs impinging onto spines with small head volumes (≤0.09 μm3) generate voltage responses and calcium signals within the spine head itself that are significantly larger than those observed in spines with larger head volumes, sufficient to activate spine BK channels and suppress EPSPs

Metástasis óseas y compresión medular como debut de carcinoma folicular de tiroides

En el carcinoma de tiroides, las metástasis a distancia son poco frecuentes (10-15% de los folículares). Los sitios más comunes son pulmón, huesos (presentación en forma de lesiones líticas), el cerebro, el hígado, la vejiga y la piel. El diagnóstico de carcinoma folicular a través de una complicación de la metástasis es excepcional, pero se debe considerar en el diagnóstico diferencial de una fractura patológica. Presentamos tres casos de aparición excepcional

Mindfulness en el síndrome de intestino irritable

The Irritable Bowel Syndrome (IBS) is a functional digestive disorder recognised as a Biopsychosocial model, because psychological, social and biological factors influence the development of its symptomatology. A high psychiatric comorbidity is frequently observed in patients with IBS associated to an increase in the severity of symptoms and a low-grade of inflammatory response. Although its pathophysiological mechanism has not been fully understood, an imbalance in bidirectional communication is described in the gut-brain axis that affects psychoneuroimmune status of IBS patients. Diverse psychotherapeutic interventions have been shown to be effective in reducing the psychosocial impact in IBS patients, as well as in reducing their intestinal symptoms. However, at the clinical practice, it is not routinely applied because of its high cost. The Mindfulness-Based Stress Reduction (MBSR) is an alternative program that shown to be effective in reducing the clinical severity and improving the quality of life of patients with IBS. Although MBSR has demonstrated to reduce the levels of pro-inflammatory cytokines, including IL-6, in healthy subjects and cancer’s patients, its effect on the immune response in IBS patients remains unknown. This review discusses the pathophysiological mechanisms underlying the relationship between psychosocial disturbances, clinical symptomatology and low-grade inflammation in IBS. Based on that, we present the arguments that allow proposing the use of MBSR for the IBS treatment

Particle formation and surface processes on atmospheric aerosols: A review of applied quantum chemical calculations

Aerosols significantly influence atmospheric processes such as cloud nucleation, heterogeneous chemistry, and heavy‐metal transport in the troposphere. The chemical and physical complexity of atmospheric aerosols results in large uncertainties in their climate and health effects. In this article, we review recent advances in scientific understanding of aerosol processes achieved by the application of quantum chemical calculations. In particular, we emphasize recent work in two areas: new particle formation and heterogeneous processes. Details in quantum chemical methods are provided, elaborating on computational models for prenucleation, secondary organic aerosol formation, and aerosol interface phenomena. Modeling of relative humidity effects, aerosol surfaces, and chemical kinetics of reaction pathways is discussed. Because of their relevance, quantum chemical calculations and field and laboratory experiments are compared. In addition to describing the atmospheric relevance of the computational models, this article also presents future challenges in quantum chemical calculations applied to aerosols