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ACS Measurement Science Au Feb 2024Nitrite is a compound used as a food additive for its preservative action and coloring capability, as well as an industrial agent for its antifreezing action and for...
Nitrite is a compound used as a food additive for its preservative action and coloring capability, as well as an industrial agent for its antifreezing action and for preventing corrosion, and it is also used as a pharmaceutical in cyanide detoxification therapy. However, even recently, because of its high toxicity, it has been used as a murder and suicidal agent due to its affordability and ready availability. In this technical report, we describe an electrochemical paper-based device for selectively determining nitrite in complex biofluids, such as blood, cadaveric blood, vitreous humor, serum, plasma, and urine. The approach was validated in terms of the linearity of response, selectivity, and sensitivity, and the accuracy of the determination was verified by comparing the results with a chromatographic instrumental method. A linear response was observed in the micromolar range; the sensitivity of the method expressed as the limit of detection was 0.4 μM in buffer measurements. The simplicity of use, the portability of the device, and the performance shown make the approach suitable for detecting nitrite in complex biofluids, including contexts of forensic interest, such as murders or suicides in which nitrite is used as a toxic agent. Limits of detection of ca. 1, 2, 4, 5, 3, and 4 μM were obtained in vitreous humor, urine, serum and plasma, blood, and cadaveric blood, also highlighting a satisfactory accuracy comprised between 91 and 112%.
PubMed: 38404486
DOI: 10.1021/acsmeasuresciau.3c00050 -
Experimental Eye Research Apr 2024Extracellular vesicles (EVs) are released as highly stable lipid bilayer particles carrying proteins, lipids, glycans and miRNAs. The contents of EVs vary based on the... (Review)
Review
Extracellular vesicles (EVs) are released as highly stable lipid bilayer particles carrying proteins, lipids, glycans and miRNAs. The contents of EVs vary based on the cellular origin, biogenesis route and the functional state of the cell suggesting certain diseased conditions. A growing body of evidence show that EVs carry important molecules implicated in the development and progression of ophthalmic diseases. EVs associated with ophthalmic diseases are mainly carried by one of the three ocular biofluids which include tears, aqueous humor and vitreous humor. This review summarizes the list of EV derived biomarkers identified thus far in ocular fluids for ophthalmic disease diagnosis. Further, the methods used for sample collection, sample volume and the sample numbers used in these studies have been highlighted. Emphasis has been given to describe the EV isolation and the characterization methods used, EV size profiled and the EV concentrations analyzed by these studies, thus providing a roadmap for future EV biomarker studies in ocular fluids.
Topics: Extracellular Vesicles; Biomarkers; MicroRNAs; Proteins; Body Fluids
PubMed: 38401855
DOI: 10.1016/j.exer.2024.109831 -
Pharmaceuticals (Basel, Switzerland) Jan 2024BI-X, a therapeutic protein under development for the treatment of human ocular disease via intravitreal administration, binds to its therapeutic targets and endogenous...
BI-X, a therapeutic protein under development for the treatment of human ocular disease via intravitreal administration, binds to its therapeutic targets and endogenous albumin in the vitreous humor. A monkey ocular pharmacokinetic (PK) study following BI-X administration was conducted to measure drug and albumin levels in plasma, the vitreous humor, the aqueous humor, and retina tissue at various timepoints post-dose. A comprehensive bioanalytical approach was implemented in support of this study. Five immunocapture-LC-MS/MS assays were developed and qualified for quantitating BI-X in different matrices, while ELISA was used for albumin measurement. Immunocapture at the protein or peptide level was evaluated to achieve adequate assay sensitivity. Drug and albumin assays were applied for the analysis of the monkey study samples.
PubMed: 38399408
DOI: 10.3390/ph17020193 -
Epidemiologia (Basel, Switzerland) Jan 2024Theories of myopia etiology based on near work and lack of outdoor exposure have had inconsistent support and have not prevented the rising prevalence of global myopia....
Theories of myopia etiology based on near work and lack of outdoor exposure have had inconsistent support and have not prevented the rising prevalence of global myopia. New scientific theories in the cause and prevention of myopia are needed. Myopia prevalence is low in native people consuming traditional diets lacking in sodium chloride, and nutritional epidemiological evidence supports the association of rising myopia prevalence with dietary sodium intake. East Asian populations have among the highest rates of myopia associated with high dietary sodium. Similar associations of sodium and rising myopia prevalence were observed in the United States in the late 20th century. The present perspective synthesizes nutritional epidemiology evidence with pathophysiological concepts and proposes that axial myopia occurs from increased fluid retention in the vitreous of the eye, induced by dietary sodium chloride intake. Salt disturbs ionic permeability of retinal membranes, increases the osmotic gradient flow of fluid into the vitreous, and stretches ocular tissue during axial elongation. Based on the present nutritional epidemiology evidence, experimental research should investigate the effect of sodium chloride as the cause of myopia, and clinical research should test a very low-salt diet in myopia correction and prevention.
PubMed: 38390916
DOI: 10.3390/epidemiologia5010003 -
Molecules (Basel, Switzerland) Jan 2024Triamcinolone acetonide (TA), a medium-potency synthetic glucocorticoid, is primarily employed to treat posterior ocular diseases using vitreous injection. This study...
Triamcinolone acetonide (TA), a medium-potency synthetic glucocorticoid, is primarily employed to treat posterior ocular diseases using vitreous injection. This study aimed to design novel ocular nanoformulation drug delivery systems using PLGA carriers to overcome the ocular drug delivery barrier and facilitate effective delivery into the ocular tissues after topical administration. The surface of the PLGA nanodelivery system was made hydrophilic (2-HP-β-CD) through an emulsified solvent volatilization method, followed by system characterization. The mechanism of cellular uptake across the corneal epithelial cell barrier used rhodamine B (Rh-B) to prepare fluorescent probes for delivery systems. The triamcinolone acetonide (TA)-loaded nanodelivery system was validated by in vitro release behavior, isolated corneal permeability, and in vivo atrial hydrodynamics. The results indicated that the fluorescent probes, viz., the Rh-B-(2-HP-β-CD)/PLGA NPs and the drug-loaded TA-(2-HP-β-CD)/PLGA NPs, were within 200 nm in size. Moreover, the system was homogeneous and stable. The in vitro transport mechanism across the epithelial barrier showed that the uptake of nanoparticles was time-dependent and that NPs were actively transported across the epithelial barrier. The in vitro release behavior of the TA-loaded nanodelivery systems revealed that (2-HP-β-CD)/PLGA nanoparticles could prolong the drug release time to up to three times longer than the suspensions. The isolated corneal permeability demonstrated that TA-(2-HP-β-CD)/PLGA NPs could extend the precorneal retention time and boost corneal permeability. Thus, they increased the cumulative release per unit area 7.99-fold at 8 h compared to the suspension. The pharmacokinetics within the aqueous humor showed that (2-HP-β-CD)/PLGA nanoparticles could elevate the bioavailability of the drug, and its was 51.91 times higher than that of the triamcinolone acetonide aqueous solution. Therefore, (2-HP-β-CD)/PLGA NPs can potentially elevate transmembrane uptake, promote corneal permeability, and improve the bioavailability of drugs inside the aqueous humor. This study provides a foundation for future research on transocular barrier nanoformulations for non-invasive drug delivery.
Topics: Polymers; Drug Carriers; 2-Hydroxypropyl-beta-cyclodextrin; Triamcinolone Acetonide; Fluorescent Dyes; Cornea; beta-Cyclodextrins; Nanoparticles; Dieldrin
PubMed: 38338402
DOI: 10.3390/molecules29030658 -
Heliyon Feb 2024Assessment and validation of endothelial-mesenchymal transition (EndoMT) in the retinal endothelium of patients with proliferative diabetic retinopathy (PDR) at the...
BACKGROUND
Assessment and validation of endothelial-mesenchymal transition (EndoMT) in the retinal endothelium of patients with proliferative diabetic retinopathy (PDR) at the level of retinal and vitreous specimens, and preliminary discussion of its regulatory mechanisms.
METHODS
Transcriptome sequencing profiles of CD31 cells from 9 retinal fibrovascular mem-branes (FVMs) and 4 postmortem retinas were downloaded from GEO databases to analyze EndoMT-related differentially expressed genes (DEGs). Then, 42 PDR patients and 34 idiopathic macular holes (IMH) patients were enrolled as the PDR and control groups, respectively. Vitreous humor (VH) samples were collected, and the expression of EndoMT-related proteins was quantified by enzyme-linked immunosorbent assay.
RESULTS
A total of 5845 DEGs were identified, and we subsequently focused on the analysis of 24 EndoMT-related marker genes, including the trigger of EndoMT, endothelial genes, mesenchymal genes, transcription factors, inflammatory factors, and autophagy markers. Six of these genes were selected for protein assay validation in VH, showing increased mesenchymal marker (type I collagen α 2 chain, COL1A2) and decreased endothelial marker (VE-cadherin, CDH5) accompanied by increased TGFβ, IL-1β, LC3B and P62 in PDR patients. In addition, anti-VEGF therapy could enhance EndoMT-related phenotypes.
CONCLUSIONS
EndoMT may underlie the pathogenesis of PDR, and the induction and regulation correlate with autophagy defects and the inflammatory response.
PubMed: 38327444
DOI: 10.1016/j.heliyon.2024.e25166 -
Frontiers in Immunology 2024Acute retinal necrosis (ARN) is an inflammatory disease that is primarily caused by herpesvirus infection, most commonly varicella-zoster virus (VZV), followed by herpes... (Review)
Review
Acute retinal necrosis (ARN) is an inflammatory disease that is primarily caused by herpesvirus infection, most commonly varicella-zoster virus (VZV), followed by herpes simplex virus (HSV) and occasionally cytomegalovirus (CMV). Sintilimab is an immune checkpoint inhibitor (ICI) that can enhance the body's anti-tumor immune response. However, treatment with ICIs may lead to reactivation of the VZV. Here, we present a case of ARN caused by VZV infection in a patient receiving sintilimab for cervical cancer. A 64-year-old female patient developed vision loss and floaters with left eye redness for one week after 22 cycles of sintilimab for cervical cancer. Based on clinical manifestations, ophthalmological examination, and vitreous humor biopsy, the patient was diagnosed with acute retinal necrosis syndrome secondary to VZV. After receiving systemic antiviral and anti-inflammatory therapy, retinal necrosis lesions and visual function improved. In conclusion, clinicians should be aware of the risk of ARN when using sintilimab and should actively monitor patients for prompt diagnosis and optimal management of this rare adverse drug reaction.
Topics: Female; Humans; Middle Aged; Retinal Necrosis Syndrome, Acute; Uterine Cervical Neoplasms; Herpesvirus 3, Human; Herpes Simplex; Antibodies, Monoclonal, Humanized
PubMed: 38322266
DOI: 10.3389/fimmu.2024.1301329 -
Investigative Ophthalmology & Visual... Feb 2024To sequence, identify, and perform phylogenetic and recombination analysis on three clinical adenovirus samples taken from the vitreous humor at the Bascom Palmer Eye...
PURPOSE
To sequence, identify, and perform phylogenetic and recombination analysis on three clinical adenovirus samples taken from the vitreous humor at the Bascom Palmer Eye Institute.
METHODS
The PacBio Sequel II was used to sequence the genomes of the three clinical adenovirus isolates. To identify the isolates, a full genome-based multiple sequence alignment (MSA) of 722 mastadenoviruses was generated using multiple alignment using fast Fourier transform (MAFFT). MAFFT was also used to generate genome-based human adenovirus B (HAdV-B) MSAs, as well as HAdV-B fiber, hexon, and penton protein-based MSAs. To examine recombination within HAdV-B, RF-Net 2 and Bootscan software programs were used.
RESULTS
In the course of classifying three new atypical ocular adenovirus samples, taken from the vitreous humor, we found that all three isolates were HAdV-B species. The three Bascom Palmer HAdV-B genomes were then combined with over 300 HAdV-B genome sequences, including nine ocular HAdV-B genome sequences. Attempts to categorize the penton, hexon, and fiber serotypes using phylogeny of the three Bascom Palmer samples were inconclusive due to incongruence between serotype and phylogeny in the dataset. Recombination analysis using a subset of HAdV-B strains to generate a hybridization network detected recombination between nonhuman primate and human-derived strains, recombination between one HAdV-B strain and the HAdV-E outgroup, and limited recombination between the B1 and B2 clades.
CONCLUSIONS
The discordance between serotype and phylogeny detected in this study suggests that the current classification system does not accurately describe the natural history and phylogenetic relationships among adenoviruses.
Topics: Humans; Animals; Adenoviridae; Vitreous Body; Phylogeny; Serogroup; Adenoviruses, Human; Hexamethonium; Recombination, Genetic
PubMed: 38319669
DOI: 10.1167/iovs.65.2.12 -
Indian Journal of Ophthalmology May 2024Some anterior chambers do not readily shallow because of insufficient posterior pressure and/or very deep anterior chamber anatomy, which can make unscrolling descemet...
Some anterior chambers do not readily shallow because of insufficient posterior pressure and/or very deep anterior chamber anatomy, which can make unscrolling descemet membrane endothelial keratoplasty (DMEK) tissue more challenging with an unmodified tap technique. We present a hands-free method for augmenting posterior pressure by temporarily tucking cellulose sponges under the blades of the eyelid speculum. The sponges transfer some of the eyelid speculum's weight onto the bulbar surface posterior to the iris, thereby indenting the sclera and causing the iris diaphragm to bulge further forward. This hands-free technique can transform a potentially challenging DMEK case into a more straightforward one by facilitating both a shallow anterior chamber and a bimanual unscrolling technique. However, it only works in bicameral eyes with a vitreous body (e.g., an eye with penetrating keratoplasty, vitreous syneresis, and axial myopia) and will not work in unicameral eyes after vitrectomy (e.g., an eye with an Anterior Chamber Intraocular Lens (ACIOL)).
Topics: Humans; Descemet Stripping Endothelial Keratoplasty; Anterior Chamber; Cellulose; Intraocular Pressure; Visual Acuity
PubMed: 38317304
DOI: 10.4103/IJO.IJO_1385_23 -
Biomedicine & Pharmacotherapy =... Mar 2024Vitreous replacement is a commonly employed method for treating a range of ocular diseases, including posterior vitreous detachment, complex retinal detachment, diabetic... (Review)
Review
Vitreous replacement is a commonly employed method for treating a range of ocular diseases, including posterior vitreous detachment, complex retinal detachment, diabetic retinopathy, macular hole, and ocular trauma. Various clinical substitutes for vitreous include air, expandable gas, silicone oil, heavy silicone oil, and balanced salt solution. However, these substitutes have drawbacks such as short retention time, cytotoxicity, high intraocular pressure, and the formation of cataracts, rendering them unsuitable for long-term treatment. Polymeric hydrogels possess the potential to serve as ideal vitreous substitutes due to their structure-mimicking to natural vitreous and adjustable mechanical properties. Replacement with hydrogels as the tamponade can help maintain the shape of the eyeball, apply pressure to the detached retina, and ensure the metabolic transport of substances without impairing vision. This literature review examines the required properties of artificial vitreous, including the optical properties, rheological properties, expansive force action, and physiological and biochemical functions of chemically and physically crosslinked hydrogels. The strategies for enhancing the biocompatibility and injectability of hydrogels are also summarized and discussed. From a clinical ophthalmology perspective, this paper presents the latest developments in vitreous replacement, providing clinicians with a comprehensive understanding of hydrogel clinical applications, which offers guidance for future design directions and methodologies for hydrogel development.
Topics: Humans; Hydrogels; Eye; Cataract; Diabetic Retinopathy; Ophthalmology; Polymers
PubMed: 38306844
DOI: 10.1016/j.biopha.2024.116154