RESUMEN

BACKGROUND: Infection in acute-on-chronic liver failure (ACLF) patients is known to cause higher mortality. The current approach is to culture all patient samples. There are no published data evaluating fungal infections in acutely decompensated patients. In this study, we aim to identify clinical factors predictive of infections within ACLF patients and assess workup compliance within 24 h of hospital admission. METHODS: We retrospectively analyzed the charts of 457 ACLF patients seen at the University of Arizona between January 1, 2014 and December 31, 2014. We used logistic regression to identify potential risk indicators for bacterial, fungal, and any infections. In order to proceed to a systemic infection workup, the following parameters were assessed: complete blood count, urinalysis, urine culture, bacterial blood culture, chest X-ray, and ascitic fluid analysis in patients with ascites. Additionally, serological markers were also assessed in patient samples. Systemic inflammatory response syndrome (SIRS) was defined as the presence of two or more of the following criteria: temperature > 38 °C or < 36 °C, heart rate > 90 beats/min, respiratory rate > 20 breaths/min, white blood cell count > 12,000 or < 4,000 cells/mm or > 10% bands. RESULTS: An established infection was observed in 60.61% of ACLF patients. SIRS criteria predicted infections with concordance statistic (C-statistic) of 0.71 (odds ratio (OR) 6.85, 95% confidence interval (CI): 4.33, 10.85) for any infection, 0.63 (OR 2.88, 95% CI: 1.96, 4.23) for bacterial infection, and 0.53 (OR 1.32, 95% CI: 0.59, 2.96) for fungal infection. After including other significant variables (over 10 additional variables), predictive ability improved, C-statistic 0.83 (95% CI: 0.77, 0.90) for any infection and 0.71 (95% CI: 0.65, 0.77) for bacterial infections. The combination of model for end-stage liver disease (MELD) and hemoglobin (Hb) predicted fungal infections with C-statistic 0.74 (95% CI: 0.63, 0.84). Workup within 24 h of admission was obtained in 12% of patients. CONCLUSIONS: Fungal infections in ACLF patients results in an increased mortality rate. Elevated MELD and low Hb in combination predict fungal infections. Compliance is very poor to obtain diagnostic workup efficiently, better tools are needed to predict infection upon admission.

RESUMEN

Diabetic retinopathy is now well understood as a neurovascular disease. Significant deficits early in diabetes are found in the inner retina that consists of bipolar cells that receive inputs from rod and cone photoreceptors, ganglion cells that receive inputs from bipolar cells, and amacrine cells that modulate these connections. These functional deficits can be measured in vivo in diabetic humans and animal models using the electroretinogram (ERG) and behavioral visual testing. Early effects of diabetes on both the human and animal model ERGs are changes to the oscillatory potentials that suggest dysfunctional communication between amacrine cells and bipolar cells as well as ERG measures that suggest ganglion cell dysfunction. These are coupled with changes in contrast sensitivity that suggest inner retinal changes. Mechanistic in vitro neuronal studies have suggested that these inner retinal changes are due to decreased inhibition in the retina, potentially due to decreased gamma aminobutyric acid (GABA) release, increased glutamate release, and increased excitation of retinal ganglion cells. Inner retinal deficits in dopamine levels have also been observed that can be reversed to limit inner retinal damage. Inner retinal targets present a promising new avenue for therapies for early-stage diabetic eye disease.

Asunto(s)

RESUMEN

A correction to this article has been published and is linked from the HTML version of this paper. The error has been fixed in the paper.

RESUMEN

In the eye, intraocular pressure (IOP) is tightly regulated and its persistent increase leads to ocular hypertension and glaucoma. We have previously shown that trabecular meshwork (TM) cells might detect aqueous humor fluid shear stress via interaction of the extracellular matrix (ECM) protein cochlin with the cell surface bound and stretch-activated channel TREK-1. We provide evidence here that interaction between both proteins are involved in IOP regulation. Silencing of TREK-1 in mice prevents the previously demonstrated cochlin-overexpression mediated increase in IOP. Biochemical and electrophysiological experiments demonstrate that high shear stress-induced multimeric cochlin produces a qualitatively different interaction with TREK-1 compared to monomeric cochlin. Physiological concentrations of multimeric but not monomeric cochlin reduce TREK-1 current. Results presented here indicate that the interaction of TREK-1 and cochlin play an important role for maintaining IOP homeostasis. [Corrected].

RESUMEN

The main and only modifiable risk factor in glaucoma, the group of usually late onset progressive and irreversible blinding optic neuropathies, is elevated intraocular pressure (IOP). The increase in IOP is due to impeded aqueous humor (AH) outflow through the conventional pathway. The aberrant increased resistance at the trabecular meshwork (TM), the filter-like region in the anterior eye chamber is the major contributory factor in causing the impeded outflow. In normal as well as in glaucoma eyes the regions of the TM are divided into areas of high and low flow. The collector channels and distal outflow regions are now increasingly being recognized as potential players in contributing to impede AH outflow. Structural and molecular make-up contributing to the segmental blockage to outflow is likely to provide greater insight. Establishing segmental blockage to outflow in model systems of glaucoma such as the mouse in parallel to human eyes will expand our repertoire of tools for investigation. Further study into this area of interest has the potential to ultimately lead to the development of new therapeutics focused on lowering IOP by targeting the various components of segmental blockage of outflow in the TM and in the distal outflow region.

Asunto(s)

RESUMEN

Proteins have important functional roles in the body, which can be altered in disease states. The eye is a complex organ rich in proteins; in particular, the anterior eye is very sophisticated in function and is most commonly involved in ophthalmic diseases. Proteomics, the large scale study of proteins, has greatly impacted our knowledge and understanding of gene function in the post-genomic period. The most significant breakthrough in proteomics has been mass spectrometric identification of proteins, which extends analysis far beyond the mere display of proteins that classical techniques provide. Mass spectrometry functions as a "mass analyzer" which simplifies the identification and quantification of proteins extracted from biological tissue. Mass spectrometric analysis of the anterior eye proteome provides a differential display for protein comparison of normal and diseased tissue. In this article we present the key proteomic findings in the recent literature related to the cornea, aqueous humor, trabecular meshwork, iris, ciliary body and lens. Through this we identified unique proteins specific to diseases related to the anterior eye.

RESUMEN

PURPOSE: To determine the difference in protein glycosylation and glycosylation enzyme levels between glaucomatous and control trabecular meshwork (TM). EXPERIMENTAL DESIGN: Glaucomatous and normal donor (n = 12 each) TM tissues, lectin fluorescence, fluorophore-assisted carbohydrate analyses, and quantitative MS were used to determine the glycosylation levels. Primary TM cells and glycosylation inhibitors were used to determine their effect on cell shape and motility. RESULTS: In contrast to elevated levels of glycoproteins determined by lectin fluorescence, simultaneous hyper- and hypo-glycosylation in glaucomatous TM was revealed by fluorophore-assisted carbohydrate analyses. Analyses of enzymes showed elevation of beta-glycosidase 1 and decrease in galactosyltransferase family 6 domain containing protein 1 in the glaucomatous TM. Quantitative MS identified select protein level changes between glaucomatous and normal TM. Primary TM cells were treated with inhibitors to elicit hypo-glycosylation, which affected cell shape, motility, and fluorescent tracer transport across a layer of TM cells. CONCLUSIONS AND CLINICAL RELEVANCE: Global protein glycosylation is aberrant in glaucomatous TM compared to controls. The results presented here suggest that the alteration in global TM protein glycosylation encompassing cellular and extracellular matrix proteins contributes to glaucoma pathology likely mediated through changes in properties of TM cells.

Asunto(s)