TGF-beta(2)- and H2O2-Induced Biological Changes in Optic Nerve Head Astrocytes Are Reduced by the Antioxidant Alpha-Lipoic Acid

Background/Aims: The goal of the present study was to determine whether transforming growth factor-beta(2) (TGF-beta(2))- and oxidative stress-induced cellular changes in cultured human optic nerve head (ONH) astrocytes could be reduced by pretreatment with the antioxidant alpha-lipoic acid (LA). Methods: Cultured ONH astrocytes were treated with 1.0 ng/ml TGF-beta(2) for 24 h or 200 mu M hydrogen peroxide (H2O2) for 1 h. Lipid peroxidation was measured by a decrease in cis-pari-naric acid fluorescence. Additionally, cells were pretreated with different concentrations of LA before TGF-beta 2 or H2O2 exposure. Expressions of the heat shock protein (Hsp) alpha B-crystallin and Hsp27, the extracellular matrix (ECM) component fibronectin and the ECM-modulating protein connective tissue growth factor (CTGF) were examined with immunohistochemistry and real-time PCR analysis. Results: Both TGF-beta(2) and H2O2 increased lipid peroxidation. Treatment of astrocytes with TGF-beta(2) and H2O2 upregulated the expression of alpha B-crystallin, Hsp27, fibronectin and CTGF. Pretreatment with different concentrations of LA reduced the TGF-beta(2)- and H2O2-stimulated gene expressions. Conclusion: We showed that TGF-beta(2)- and H2O2-stimulated gene expressions could be prevented by pretreatment with the antioxidant LA in cultured human ONH astrocytes. Therefore, it is tempting to speculate that the use of antioxidants could have protective effects in glaucomatous optic neuropathy. Copyright (C) 2012 S. Karger AG, Base

Preventive Effects of Omega-3 and Omega-6 Fatty Acids on Peroxide Mediated Oxidative Stress Responses in Primary Human Trabecular Meshwork Cells

Pathologic processes in glaucoma include increased apoptosis, accumulation of extracellular material in the trabecular meshwork and optic nerve, condensations of the cytoskeleton and precocious cellular senescence. Oxidative stress was shown to generate these alterations in primary ocular cells. Fatty acids omega-3 and -6 are alleged to constitute a prophylaxis against these deleterious effects. Here, we tested actual preventive effects omega-3 and -6 against peroxide induced stress responses in primary human trabecular meshwork cells. Changes of mitochondrial activity, proliferation, heat shock proteins, extracellular matrix components, and inflammatory markers were evaluated. Alterations of the cytoskeleton were evaluated by phalloidin labeling. Here we report a repressive effect of omega-6 on metabolic activity and proliferation, which was not detected for omega-3. Both agents were able to prevent the anti-proliferative effect of H2O2, but only omega-3 prevented metabolic repression. Expression of heat shock protein 27 was unaltered by both fatty acids, whereas heat shock protein 90 was significantly induced by both. Omega-6 increased fibronectin and connective tissue growth factor synthesis, as well as the amount of secreted fibronectin. Omega-3, instead, induced plasminogen activator inhibitor 1 synthesis. H2O2 further increased fibronectin production in omega-6 supplemented cells, which was not the case in omega-3 treated cells. H2O2 stimulation of plasminogen activator inhibitor 1 and connective tissue growth factor was repressed by both fatty acids. Both fatty acids appeared to abolish H2O2 mediated stimulation of nuclear factor κB and IL-6, but not IL-1α and IL-8. H2O2 induced formation of cross-linked actin networks and stress fibers, which was reduced by preemptive application of omega-3. Omega-6, in contrast, had no protective effect on that, and even seemed to promote condensation. Based on the observed side effects of omega-6, omega-3 appears to be the more beneficial fatty acid in respect of prophylactic intake for prevention of a glaucomatous disease

Influence of taste disorders on dietary behaviors in cancer patients under chemotherapy

<p>Abstract</p> <p>Objectives</p> <p>To determine the relationship between energy and nutrient consumption with chemosensory changes in cancer patients under chemotherapy.</p> <p>Methods</p> <p>We carried out a cross-sectional study, enrolling 60 subjects. Cases were defined as patients with cancer diagnosis after their second chemotherapy cycle (n = 30), and controls were subjects without cancer (n = 30). Subjective changes of taste during treatment were assessed. Food consumption habits were obtained with a food frequency questionnaire validated for Mexican population. Five different concentrations of three basic flavors --sweet (sucrose), bitter (urea), and a novel basic taste, umami (sodium glutamate)-- were used to measure detection thresholds and recognition thresholds (RT). We determine differences between energy and nutrient consumption in cases and controls and their association with taste DT and RT.</p> <p>Results</p> <p>No demographic differences were found between groups. Cases showed higher sweet DT (6.4 vs. 4.4 μmol/ml; p = 0.03) and a higher bitter RT (100 vs. 95 μmol/ml; <it>p </it>= 0.04) than controls. Cases with sweet DT above the median showed significant lower daily energy (2,043 vs.1,586 kcal; p = 0.02), proteins (81.4 vs. 54 g/day; <it>p </it>= 0.01), carbohydrates (246 vs.192 g/day; <it>p </it>= 0.05), and zinc consumption (19 vs.11 mg/day; <it>p </it>= 0.01) compared to cases without sweet DT alteration. Cases with sweet DT and RT above median were associated with lower completion of energy requirements and consequent weight loss. There was no association between flavors DT or RT and nutrient ingestion in the control group.</p> <p>Conclusion</p> <p>Changes of sweet DT and bitter RT in cancer patients under chemotherapy treatment were associated with lower energy and nutrient ingestion. Taste detection and recognition thresholds disorders could be important factors in malnutrition development on patients with cancer under chemotherapy treatment.</p

Time-Frequency Analysis of Chemosensory Event-Related Potentials to Characterize the Cortical Representation of Odors in Humans

BACKGROUND: The recording of olfactory and trigeminal chemosensory event-related potentials (ERPs) has been proposed as an objective and non-invasive technique to study the cortical processing of odors in humans. Until now, the responses have been characterized mainly using across-trial averaging in the time domain. Unfortunately, chemosensory ERPs, in particular, olfactory ERPs, exhibit a relatively low signal-to-noise ratio. Hence, although the technique is increasingly used in basic research as well as in clinical practice to evaluate people suffering from olfactory disorders, its current clinical relevance remains very limited. Here, we used a time-frequency analysis based on the wavelet transform to reveal EEG responses that are not strictly phase-locked to onset of the chemosensory stimulus. We hypothesized that this approach would significantly enhance the signal-to-noise ratio of the EEG responses to chemosensory stimulation because, as compared to conventional time-domain averaging, (1) it is less sensitive to temporal jitter and (2) it can reveal non phase-locked EEG responses such as event-related synchronization and desynchronization. METHODOLOGY/PRINCIPAL FINDINGS: EEG responses to selective trigeminal and olfactory stimulation were recorded in 11 normosmic subjects. A Morlet wavelet was used to characterize the elicited responses in the time-frequency domain. We found that this approach markedly improved the signal-to-noise ratio of the obtained EEG responses, in particular, following olfactory stimulation. Furthermore, the approach allowed characterizing non phase-locked components that could not be identified using conventional time-domain averaging. CONCLUSION/SIGNIFICANCE: By providing a more robust and complete view of how odors are represented in the human brain, our approach could constitute the basis for a robust tool to study olfaction, both for basic research and clinicians

More Than Smell - COVID-19 Is Associated With Severe Impairment of Smell,Taste, and Chemesthesis

Recent anecdotal and scientific reports have provided evidence of a link between COVID-19 and chemosensory impairments, such as anosmia. However, these reports have downplayed or failed to distinguish potential effects on taste, ignored chemesthesis, and generally lacked quantitative measurements. Here, we report the development, implementation, and initial results of a multilingual, international questionnaire to assess self-reported quantity and quality of perception in 3 distinct chemosensory modalities (smell, taste, and chemesthesis) before and during COVID-19. In the first 11 days after questionnaire launch, 4039 participants (2913 women, 1118 men, and 8 others, aged 19-79) reported a COVID-19 diagnosis either via laboratory tests or clinical assessment. Importantly, smell, taste, and chemesthetic function were each significantly reduced compared to their status before the disease. Difference scores (maximum possible change +/- 100) revealed a mean reduction of smell (-79.7 +/- 28.7, mean +/- standard deviation), taste (-69.0 +/- 32.6), and chemesthetic (-37.3 +/- 36.2) function during COVID-19. Qualitative changes in olfactory ability (parosmia and phantosmia) were relatively rare and correlated with smell loss. Importantly, perceived nasal obstruction did not account for smell loss. Furthermore, chemosensory impairments were similar between participants in the laboratory test and clinical assessment groups. These results show that COVID-19-associated chemosensory impairment is not limited to smell but also affects taste and chemesthesis.The multimodal impact of COVID-19 and the lack of perceived nasal obstruction suggest that severe acute respiratory syndrome coronavirus strain 2 (SARS-CoV-2) infection may disrupt sensory-neural mechanisms

Evaluation of intraocular pressure elevation after multiple injections of intravitreal ranibizumab

Alice L Yu,1,* Florian Seidensticker,1,* Markus Schaumberger,1 Ulrich Welge-Lussen,2 Armin Wolf11Department of Ophthalmology, Ludwig-Maximilians-University, Munich, Germany; 2Department of Ophthalmology, Friedrich-Alexander-University, Erlangen, Germany*These authors contributed equally to this workBackground: We wanted to determine whether multiple injections of intravitreal ranibizumab was associated with an elevated intraocular pressure (IOP) in patients treated for neovascular age-related macular degeneration (AMD).Methods: This retrospective study examined 53&nbsp;patients with neovascular AMD treated with multiple injections of intravitreal ranibizumab. The main outcome measure was the difference in IOP between the frequently-treated study eyes (&ge;15&nbsp;injections) and the unfrequently-treated fellow control eyes (&le; five injections). Patients were divided into three study groups: group&nbsp;I (35&nbsp;patients with 15&nbsp;to 19&nbsp;injections); group II (15&nbsp;patients with 20&nbsp;to 29&nbsp;injections); and group&nbsp;III (three patients with &ge;30&nbsp;injections). The IOP was measured by Goldmann applanation tonometry 4&nbsp;weeks after the last injection of intravitreal ranibizumab. For statistical analysis, the IOP was then correlated with the number of ranibizumab injections.Results: Among the frequently-treated study eyes, the mean IOP was 13.68&plusmn;2.91&nbsp;mmHg (range, 8&nbsp;to 20&nbsp;mmHg). The unfrequently-treated fellow control eyes had a mean IOP of 13.45&plusmn;3.09&nbsp;mmHg (range, 9&nbsp;to 25&nbsp;mmHg). There was no significant correlation of the IOP difference between the study and control eyes with the number of ranibizumab injections (correlation coefficient 0.77; P=0.583). For each of groups I, II, and III, the difference in mean IOP between the study and control eyes was nonsignificant (P&gt;0.05). There was also no significant association of the IOP difference between the study and control eyes with the number of ranibizumab injections for each group (P=0.391).Conclusion: Our study did not find an increased IOP in frequently-ranibizumab-treated eyes when compared to unfrequently-treated fellow control eyes. Further studies with a greater sample size are needed to evaluate whether an increased number of ranibizumab injections is associated with IOP changes.Keywords: age-related macular degeneration, ocular hypertension, anti-VEGF therap

Ultrastructure of the vitreoretinal interface following plasmin assisted vitrectomy

AIMS—To investigate the ultrastructure of the vitreoretinal interface following plasmin induced posterior vitreous detachment.
METHODS—Plasmin (1 or 2 U/0.1 ml) was injected into the vitreous cavity of 24 eyes of freshly slaughtered pigs. The 24 fellow eyes received calcium-free and magnesium-free PBS and served as a control. After incubation at 37°C for 30 and 60 minutes, the globes were placed in fixative and hemisected. Specimens for light, scanning, and transmission electron microscopy were obtained from the posterior pole, the equator, and the vitreous base using a corneal trephine.
RESULTS—All plasmin treated eyes showed posterior vitreous detachment. However, the inner limiting membrane (ILM) was covered by remnants of cortical vitreous at the posterior pole and at the equator. There was a direct correlation between the concentration and exposure times of plasmin and the degree of vitreoretinal separation. Eyes exposed to 1 U plasmin for 30 minutes had a dense network of residual collagen fibrils while those exposed to 1 U plasmin for 60 minutes had only sparse collagen fibrils covering the ILM. Eyes treated with 2 U plasmin for 60 minutes had a smooth retinal surface, consistent with a bare ILM. At the vitreous base there was no vitreoretinal separation. In all control eyes the vitreous cortex was completely attached to the retina. There was no evidence of retinal damage in any plasmin treated eye.
CONCLUSION—Plasmin induces a cleavage between the vitreous cortex and the ILM without morphological changes to the retina. In contrast with previous reports, plasmin produces a smooth retinal surface and additional surgery is not required in this experimental setting. The degree of vitreoretinal separation depends on the concentration and length of exposure to plasmin.