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Brain edema is a pathological condition with potentially fatal consequences, related to cerebral injuries such as ischemia, chronic renal failure, uremia, and diabetes, among others. Under these pathological states, the cell volume control processes are fully compromised, because brain cells are unable to regulate the movement of water, mainly regulated by osmotic gradients. The processes involved in cell volume regulation are homeostatic mechanisms that depend on the mobilization of osmolytes (ions, organic molecules, and polyols) in the necessary direction to counteract changes in osmolyte concentration in response to water movement. The expression and coordinated function of proteins related to the cell volume regulation process, such as water channels, ion channels, and other cotransport systems in the glial cells, and considering the glial cell proportion compared to neuronal cells, leads to consider the astroglial network the main regulatory unit for water homeostasis in the central nervous system (CNS). In the last decade, several studies highlighted the pivotal role of glia in the cell volume regulation process and water homeostasis in the brain, including the retina; any malfunction of this astroglial network generates a lack of the ability to regulate the osmotic changes and water movements and consequently exacerbates the pathological condition.

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PURPOSE: In order to better understand cataract development, we analyzed the glycosylation profile of human lens epithelial cells (HLECs) from anterior lens capsules of type 2 diabetes mellitus (T2DM) and non-diabetic (ND) patients undergoing routine cataract surgery. SETTING: Research Department of the Asociación para Evitar la Ceguera, Hospital "Dr. Luis Sánchez Bulnes", Mexico. DESIGN: Experimental study. METHODS: Evaluation of anterior lens capsules from T2DM and ND patients undergoing phacoemulsification and free from other ocular diseases. RESULTS: Hematoxylin-eosin staining revealed HLECs alterations in T2DM samples. From lectins with different sugar specificities used, concanavalin A showed significant differences, labeling homogeneously both in the cytoplasm and in cell membranes in ND capsules, while in T2DM capsules, in addition to membrane and cytoplasm labeling, there were perinuclear vesicles with high concanavalin A labeling. Two-dimensional gel electrophoresis showed that T2DM patients have a ~65-kDa spot with an isoelectric point of 5.5 with a higher density compared to ND capsules, and liquid chromatography-tandem mass spectrometry (LC-MS/MS) analysis showed 62% homology with type-1 cytokeratin. Immunohistochemistry using anti-pan cytokeratin antibody revealed co-localization with concanavalin A, and a lectin blot revealed with concanavalin A showed a band of ~65 kDa, a molecular weight that corresponds to human type 1 cytokeratin. CONCLUSION: These results suggest that over-expression of N-glycosidically linked human type 1 cytokeratin may induce capsule disruption and affect selective permeability, allowing the entry of different molecules to the lens that facilitate cataract progression.

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The use of additives in the feed industry for producing fish has become the focus of constant change and research. The formulation of a product as a feeding strategy leads to the use of more than one molecule with particular characteristics to seek a synergistic effect when they are administered in the food. The application of taurine and silymarin in the salmon farming industry needs the exploration of the synergistic effects. For this study, we evaluated the effects of various concentrations of additives in the cell line CHSE-214 of Oncorhynchus tshawytscha. The cells were exposed to increasing concentrations of hydrogen peroxide as an oxidizing agent and were then given treatments of taurine, silymarin or both additives together. Our results indicate that the molecules had separate antioxidant effects, and the taurine treatment reached the highest number of cells per area at a dose of 100 ppm. However, if the cells were treated together at 100 ppm, silymarin achieved outstanding effects. However, when the treatment with both molecules was increased to 500 ppm of taurine, the effect was blocked, and the treatment acted as an antagonist. Our data indicate that the formulation of diets must be rigorously carried out, especially for determining the doses to be used to generate synergy among antioxidant additives and to reduce the effect of antagonism between the additives. Likewise, the use of cell lines is a strategy to evaluate the mechanisms of action for additives that are used in the development of diets for the salmon industry.

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Age-related macular degeneration (AMD) is a well-characterized and extensively studied disease. It is currently considered the leading cause of visual disability among patients over 60 years. The hallmark of early AMD is the formation of drusen, pigmentary changes at the macula, and mild to moderate vision loss. There are two forms of AMD: the "dry" and the "wet" form that is less frequent but is responsible for 90% of acute blindness due to AMD. Risk factors have been associated with AMD progression, and they are taking relevance to understand how AMD develops: (1) advanced age and the exposition to environmental factors inducing high levels of oxidative stress damaging the macula and (2) this damage, which causes inflammation inducing a vicious cycle, altogether causing central vision loss. There is neither a cure nor treatment to prevent AMD. However, there are some treatments available for the wet form of AMD. This article will review some molecular and cellular mechanisms associated with the onset of AMD focusing on feasible treatments for each related factor in the development of this pathology such as vascular endothelial growth factor, oxidative stress, failure of the clearance of proteins and organelles, and glial cell dysfunction in AMD.

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The integrin family of cell adhesion molecules mediates homeostasis, signal transduction, and various other interactions between the cell and the extracellular matrix. Integrins are type-1 transmembrane glycoproteins located on the cell surface, widely expressed in leukocytes, which play an important role in the inflammatory pathway. The purpose of this review is to summarize the current state of anti-integrin therapy and to assess ongoing clinical trials in ocular disease. We performed a search on PubMed, CINAHL, and Embase for the published literature available using the MeSH terms: "integrin therapy" and "αLß2," "α4ß1" and "α4ß7," "αvß3," "αvß5," and "αvß1" and/or "ophthalmology," and "clinical trials." We used no language restrictions. We generated searches to account for synonyms of these keywords and MESH headings as follows: (1) "integrin," "therapy," or "treatment"; (2) "clinical trials," "ophthalmology," or "ocular." In addition, the analysis included phase 2 and phase 3 clinical trials with a minimal follow-up of six months. Integrin antagonists have shown their capacity to improve signs and symptoms of patients with dry eye disease, age-related macular degeneration, diabetic macular edema, and vitreomacular traction.

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Resumen: El estrés produce la sobreactivación del eje HPA y sistema neuroendocrino. Se ha mostrado que existe daño en estructuras relacionadas con el procesamiento emocional (amígdala) aprendizaje (hipocampo), toma de decisiones y prospección (corteza prefrontal). Sin embargo, se generalizan los efectos del estrés sin ponderar el tipo de estrés (crónico o agudo), duración, especie, etc. Esto permite que hallazgos se contrapongan a nivel cortical, neuroquímico, hormonal y conductual. El objetivo fue evaluar los efectos del estrés crónico impredecible (ECI) en diferentes cepas de ratas y sus efectos inmediatos o a largo plazo. Se utilizaron ratas macho Wistar, Wistar Kyoto y SHR en condiciones estándar de laboratorio. Se aplicó una batería de ECI y una batería de evaluación conductual para evaluar efectos previos, agudos y crónicos. La cepa Wistar Kyoto muestra deficiencias previas a la exposición. La cepa SHR muestra mayor movilidad y sesgos atencionales, lo que produce un efecto que perdura a largo plazo. La cepa Wistar muestra una gran capacidad de adaptación ya que aunque se observaron deficiencias inmediatamente después de la exposición al estrés, éstas se recuperan e largo plazo. Se infiere que las precondiciones de los sujetos podrían funcionar como biomarcadores y poder prevenir padecimientos relacionados al estrés.

Abstract: Stress produces the over activation of the Hypothalamus Pituitary Adrenal axis (HPA) and the neuroendocrine system. It has been shown that it could damage structures related with the emotional processing (amygdala), learning and memory (Hippocampus), decision making and prospection (prefrontal cortex). However, the stress affects are generalized without weighting all the elements related with this conditions, for example the kind of stress stimuli (acute or chronic), duration, species, etc. This allowed that some findings it will go against each other in relation to cerebral cortex function, neurochemical, hormonal and behavioral. The main porpoise of this research was to evaluate the effects of the unpredictable chronic stress on several rat strains (Wistar, Wistar Kyoto and SHR) and its immediate effects or in long term so. Wistar, Wistar Kyoto and SHR rats were used. All animals were housed in standard laboratory conditions and we follow the international guide for use and care of laboratory animals. The subjects were exposed to the Chronic Unpredictable Stress Battery (CUSB) and to evaluate the stress effects all the subjects were evaluated with a Battery of Behavioral Evaluation to find the previous, immediate or the long-term effects of CUSB exposition. The Wistar Kyoto strain showed deficits before the stress exposure. Whereas the SHR rats showed more mobility and poor attention which produces a long-term effect. The Wistar strain show a high adaptation to the adverse conditions because until the animals showed strong effects immediately after the stress exposure they showed a good recovery in the long term. In conclusion we can asseverate that the preconditions in every strain plays a major role in the stress response and that preconditions it could be used as biomarkers and in that way infer if the subjects are more susceptible to suffer high stress or some other related disease.

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AIM: To compare the effect of phacoemulsification on intraocular pressure (IOP) in patients with primary open angle glaucoma (POAG) and pseudoexfoliation glaucoma (PXG). METHODS: A retrospective comparative case series conducted at the Glaucoma Department at the Association to Prevent Blindness in Mexico. The study enrolled consecutive patients having phacoemulsification with intraocular lens (IOL) implantation and a diagnosis of POAG or PXG. Data about IOP values and number of glaucoma medications used was collected at baseline, 1, 3, 6 and 12mo postoperatively. RESULTS: The study enrolled 88 patients (88 eyes). After phacoemulsification, there was a statistically significant reduction in IOP values and glaucoma medications use compared to baseline in both POAG and PXG patients (P<0.001). In the POAG group, a 20% decrease in IOP values was evidenced, and a 56.5% reduction in the number of medications used at the one-year follow-up. The PXG group showed a 20.39%, and a 34.46% decrease in IOP and number of medications used, respectively. A significant difference in the mean ΔIOP (postoperative changes in IOP) was evidenced between groups (P=0.005). The reduction of the postsurgical IOP mean values in both groups, the POAG group showed a greater reduction in IOP values compared to the PXG group. CONCLUSION: In both types of glaucoma, phacoemulsification cataract surgery can result in a significant IOP reduction (20%) over a 12mo follow-up period. The number of medications used is also significantly reduced up to 12mo after surgery, especially in the PXG group.

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Alzheimer's disease severely compromises cognitive function. One of the mechanisms to explain the pathology of Alzheimer's disease has been the hypotheses of amyloid-pore/channel formation by complex Aß-aggregates. Clinical studies suggested the moderate alcohol consumption can reduces probability developing neurodegenerative pathologies. A recent report explored the ability of ethanol to disrupt the generation of complex Aß in vitro and reduce the toxicity in two cell lines. Molecular dynamics simulations were applied to understand how ethanol blocks the aggregation of amyloid. On the other hand, the in silico modeling showed ethanol effect over the dynamics assembling for complex Aß-aggregates mediated by break the hydrosaline bridges between Asp 23 and Lys 28, was are key element for amyloid dimerization. The amyloid pore/channel hypothesis has been explored only in neuronal models, however recently experiments suggested the frog oocytes such an excellent model to explore the mechanism of the amyloid pore/channel hypothesis. So, the used of frog oocytes to explored the mechanism of amyloid aggregates is new, mainly for amyloid/pore hypothesis. Therefore, this experimental model is a powerful tool to explore the mechanism implicates in the Alzheimer's disease pathology and also suggests a model to prevent the Alzheimer's disease pathology.

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Here, we describe an outward rectifying current in Xenopus tropicalis oocytes that we have called xtClC-or. The current has two components; the major component is voltage activated and independent of intracellular or extracellular Ca(2+), whereas the second is a smaller component that is Ca(2+) dependent. The properties of the Ca(2+)-independent current, such as voltage dependence and outward rectification, resemble those of ClC anion channels/transporters. This current is sensitive to NPPB and NFA, insensitive to 9AC and DIDS, and showed a whole-cell conductance sequence of SCN(-)>I(-)>Br(-)>CI(-). RT-PCR revealed the expression in oocytes of ClC-2 to ClC-7, and major reductions of current amplitudes were observed when a ClC-5 antisense oligonucleotide was injected into oocytes. The Ca(2+)-dependent component was abated after injection of 10mM BAPTA or EGTA, whereas 10mMMg(2+) inhibited the current to 26±3.1%. This component was blocked by 9-AC, NFA, and NPPB, whereas DIDS did not elicit any evident effect. The ion sequence selectivity was SCN=I(-)>Br(-)>Cl(-). To try to determine the molecular identity that gives rise to this component we assessed by RT-PCR the expression of the Ca(2+)-dependent Cl(-) channel TMEM16A, which was found to be present in the oocytes. However, injection of antisense TMEM16A oligonucleotides did not inhibit the transient outward current. This result fits well with the electrophysiological data. Together, these results suggest that ClC-5 is a major, but not the sole channel responsible for this outwardly rectifying Cl(-) current.

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Xenopus laevis oocytes exposed to amyloid-ß aggregate generated oscillatory electric activity (blips) that was recorded by two-microelectrode voltage-clamp. The cells exhibited a series of "spontaneous" blips ranging in amplitude from 3.8 ± 0.9 nA at the beginning of the recordings to 6.8 ± 1.7 nA after 15 min of exposure to 1 µM aggregate. These blips were similar in amplitude to those induced by the channel-forming antimicrobial agents amphotericin B (7.8 ± 1.2 nA) and gramicidin (6.3 ± 1.1 nA). The amyloid aggregate-induced currents were abolished when extracellular Ca(2+) was removed from the bathing solution, suggesting a central role for this cation in generating the spontaneous electric activity. The amyloid aggregate also affected the Ca(2+)-dependent Cl(-) currents of oocytes, as shown by increased amplitude of the transient-outward chloride current (T(out)) and the serum-activated, oscillatory Cl(-) currents. Electron microcopy revealed that amyloid aggregate induced the dissociation of the follicular cells that surround the oocyte, thus leading to a failure in the electro-chemical communication between these cells. This was also evidenced by the suppression of the oscillatory Ca(2+)-dependent ATP-currents, which require proper coupling between oocytes and the follicular cell layer. These observations, made using the X. laevis oocytes as a versatile experimental model, may help to understand the effects of amyloid aggregate on cellular communication.

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