Search

Introduction: Hepatic glycogen storage diseases (GSDs) are a group of inherited disorders of carbohydrate metabolism for which dietary management is the cornerstone. Safety and acute complications associated with dietary management have been poorly documented. We hypothesized that safety issues and complications associated with dietary management are prevalent amongst patients with these ultra-rare disorders., Methods: A questionnaire was developed consisting of 40 questions and was distributed via eight GSD patient organizations from multiple countries. Respondents were (caregivers of) patients with self-reported hepatic GSD., Results: 249 GSD patients from 26 countries responded with a median age of 14.8 years (range: 0.5-66.1). Although management was considered safe by 71% of patients, 51% reported at least one acute complication associated with dietary management, with a total number of 425 reported complications. Most frequently reported causes were: not waking up by an alarm clock (n = 70), forgetting a meal (n = 57) and infections (n = 43). Most frequently reported complications were: hypoglycemia (n = 112), hospital admissions (n = 79) and drowsiness (n = 74). Most complications occurred before the age of 12 years (82%; 637/774 total number of reported events) and during night time (63%; 340/536). Only 61% (152/249) of the GSD patients reported using a written emergency protocol., Conclusions: Safety issues and complications associated with dietary management are prevalently reported by (caregivers of) 249 GSD patients. A discrepancy has been observed between the patient's perspective on safety of dietary management and occurrence of complications as a result of dietary management., (Copyright © 2018 The Authors. Published by Elsevier Inc. All rights reserved.)

The aim of this study was to evaluate the in vitro and in vivo susceptibility of Trypanosoma evansi to α-Bisabolol and solid lipid nanoparticles containing α-Bisabolol (SLN-B). In vitro, a trypanocidal effect of α-Bisabolol and SLN-B was observed when used at 0.5, 1 and 2% concentrations, i.e., the concentrations of 1 and 2% showed a faster trypanocidal effect when compared to chemotherapy (diminazene aceturate - D.A.). T. evansi infected mice were treated with α-Bisabolol and SLN-B at a dose of 1.0 mL kg -1 during seven days via oral gavage. In vivo, treatment with SLN-B, D.A. and D.A. associated with SLN-B were able to increase (p < 0.05) the pre-patent period and longevity when compared to positive control (infected and untreated animals), but showed no curative efficacy. T. evansi infected mice treated with D.A. associate with SLN-B, where a curative efficacy of 50% was found, a much better result when D. A and SLN-B were used alone (16.66%). In summary, the association with D. A + SLN-B can be used as an alternative to improve the therapeutic effectiveness of D.A., and for treatment of infected animals with T. evansi. Also, the nanotechnology associated with natural products arises an important alternative for the improve the trypanocidal action., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Macromolecular cell markers are essential for the classification and characterization of the highly complex and cellularly diverse vertebrate retina. Although a plethora of markers are described in the current literature, the immunoreactivity of these markers in normal human tissue has not been fully determined. This is problematic as they are quintessential to the characterization of morphological changes associated with human retinal disease. This review provides an overview of the macromolecular markers currently available to assess human retinal cell types. We draw on immunohistochemical studies conducted in our laboratories to describe marker immunoreactivity in human retina alongside comparative descriptions in non-human tissues. Considering the growing number of eye banks services offering healthy and diseased human retinal tissue, this review provides a point of reference for future human retina studies and highlights key species specific disease applications of some macromolecular markers., (Copyright © 2016 Elsevier Ltd. All rights reserved.)

Rhegmatogenous retinal detachment is by far the most common indication for retinal surgery and a major cause of severe vision loss. Increased levels of glutamate found in the vitreous of human patients and persistent remodeling, even after reattachment, suggest substantial neurochemical, functional and anatomical changes have occurred in the detached retina. Therefore, this study was designed to characterize the morphological changes and glutamate receptor functionality in human rhegmatogenous retinal detachment. A cation channel permeating probe, agmatine (1-amino-4-guanidobutane; AGB), was employed to track endogenous and kainate (KA) driven channel functionality combined with immunocytochemical characterization of cellular remodeling. In the detached retina increased AGB permeability was identified in the outer retina while there was a decrease in the inner retina in basal conditions. KA receptors exhibited increased AGB permeability in ON bipolar cells and decreased permeability in calbindin labeled inner retinal cells. All retinal detachment samples demonstrated ectopic synaptic protein expression, photoreceptor processes extending toward the inner retina, and other remodeling features of retinal degeneration. These anatomical changes have been demonstrated in animal studies and are novel features unreported in primary cases of human retinal detachment. We conclude that deafferentation in retinal detachment leads to alteration of the glutamatergic pathway., (Copyright © 2012 Elsevier Ltd. All rights reserved.)

Glutamate is the major neurotransmitter in the vertebrate retina. Neurons involved in the glutamate pathway express α-amino-3-hydroxyl-5-methylisoxazole-4-propionic acid (AMPA), kainic acid (KA) and N-methyl-D-aspartate (NMDA) receptors. Functional characterization of these ionotropic glutamate receptors can be achieved by using a cation channel permeating probe named agmatine (1-amino-4-guanidobutane; AGB). Retinal mapping using this guanidinium analog has certain advantages including the immunocytochemical identification of a whole population of neurons expressing functional glutamate gated receptor channels. We have extended AGB studies into the functionality of ionotropic receptors in peripheral aged human retina to serve as a comparison for functional analysis of retinopathies such as retinal detachment. We probed the human retina with AGB after activation with AMPA, KA and NMDA. The results showed patterns of AGB entry into neurons consistent with those previously observed in subunit localization studies in adult mammalian retinae including primates. Application of 30 μM AMPA activated receptors in virtually all calretinin immunoreactive AII amacrine cells in the mid-peripheral human retina. About half of the AII amacrine cells showed AGB permeation after incubation with 50 μM KA. Some bipolar cells including DB3 OFF bipolar cells displayed functional KA receptors. Colocalization of AGB with parvalbumin labeled horizontal cells revealed functional KA and AMPA receptors with no responsiveness to NMDA activation. NMDA activation resulted in AGB labeling of ganglion cells and amacrine cells. The present study provides a description of functional ionotropic glutamate receptors in the aged mid-peripheral human retina., (Copyright © 2011 Elsevier Ltd. All rights reserved.)