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Journal of Analytical Toxicology Apr 2020Gamma-hydroxybutyrate (GHB) is a naturally occurring molecule present in the human body as a catabolite of the neurotransmitter gamma-aminobutyrate (GABA). In the USA,...
Gamma-hydroxybutyrate (GHB) is a naturally occurring molecule present in the human body as a catabolite of the neurotransmitter gamma-aminobutyrate (GABA). In the USA, GHB has a history of being manufactured illicitly and abused, with misguided proposed benefits for the body-building community and a persistent party drug with reported GHB overdoses occurring worldwide. The interpretation of GHB in postmortem biological fluids is complicated by the endogenous nature of the molecule. Analysis often requires more than one biological matrix to detect exogenous exposure, typically in urine. The analysis is further complicated by the endogenous de novo production of GHB in postmortem specimens. This work sought to examine the prevalence of endogenous GHB concentrations in postmortem toxicology samples from Orange County, CA, and to establish suitable in-house secondary matrices to confirm or rule out exogenous GHB exposure. A total of 348 postmortem heart blood samples were randomly selected and analyzed for GHB using liquid-liquid extraction followed by gas chromatography-mass spectrometry with selective ion monitoring and GHB-d6 as an internal standard. Of the 348 cases analyzed, 39 cases resulted in positive GHB detection with the median concentration of 22.45 mg/L (10.4-62.16 mg/L). None of the positive samples had suspected GHB ingestion or usage from the case report. GHB concentrations were then examined in secondary matrices collected at autopsy from the positive cases that included (when available) peripheral blood, urine, vitreous humor, liver homogenate and brain homogenate. Within the secondary matrices, GHB levels in peripheral blood compared to that of heart blood, while liver homogenate levels were variable. Quantifiable GHB levels were not identified in vitreous humor and brain homogenate samples. Our findings reaffirm the importance of multi-matrix analysis in postmortem toxicology and further confirm the utility of vitreous humor and brain tissue to distinguish exogenous GHB exposure from endogenous production.
Topics: Autopsy; Body Fluids; Humans; Illicit Drugs; Postmortem Changes; Sodium Oxybate; Substance Abuse Detection; Vitreous Body
PubMed: 31776561
DOI: 10.1093/jat/bkz094 -
Journal of Forensic and Legal Medicine Oct 2021Vitreous humor has been extensively used in forensic practice to assess hyperglycemia after death. The results from different articles, for various hyperglycemia markers... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Vitreous humor has been extensively used in forensic practice to assess hyperglycemia after death. The results from different articles, for various hyperglycemia markers are highly variable, and a systematic analysis of the results from studies currently used in forensic practice as landmarks has not yet been performed. Therefore, we aimed to evaluate to usefulness and limits of using the values of vitreous glucose, lactic acid, beta-hydroxybutyrate, and 1,5 Anhydro-d-glucitol to detect postmortem hyperglycemia.
MATERIALS AND METHODS
For this purpose, we performed a systematic review and a meta-analysis using the random-effects model to identify the threshold values and average differences for the markers mentioned above in the vitreous humor of diabetic versus nondiabetic subjects.
RESULTS
We included eleven studies in the meta-analysis and found the following mean differences between the diabetic and nondiabetic groups: for glucose - 91.4 mg/dl, for lactate - 34.17 mg/dl, for the Traub formula - 111 mg/dl, for fructosamine - 0.71 mmol/L, for beta-hydroxybutyrate - 36.55 mg/dl and 1,5 Anhydro-d-glucitol - -15.2 mg/dl. We also gave practical recommendations, based on the range of values and 95% confidence intervals in normal subjects and controls to identify antemortem hyperglycemia and evaluated, whenever possible, threshold values for fatal diabetes.
CONCLUSIONS
Glucose, Traub formula, fructosamine, and beta-hydroxy-butyrate can be used to detect postmortem hyperglycemia with some limitations; 1,5 Anhydro-d-glucitol can only be used to suggest the absence of a hyperglycemic status before death.
Topics: 3-Hydroxybutyric Acid; Biomarkers; Deoxyglucose; Forensic Medicine; Fructosamine; Glucose; Humans; Hyperglycemia; Lactic Acid; Postmortem Changes; Vitreous Body
PubMed: 34488176
DOI: 10.1016/j.jflm.2021.102250 -
Forensic Science International May 2020The chemical and biochemical analysis of bodily fluids after death is an important thanatochemical approach to assess the cause and time since death. Vitreous humor (VH)... (Review)
Review
The chemical and biochemical analysis of bodily fluids after death is an important thanatochemical approach to assess the cause and time since death. Vitreous humor (VH) has been used as a biofluid for forensic purposes since the 1960s. Due to its established relevance in toxicology, a literature review highlighting the use of VH with an emphasis on endogenous compounds has not yet been undertaken. VH is a chemically complex aqueous solution of carbohydrates, proteins, electrolytes and other small molecules present in living organisms; this biofluid is useful tool for its isolated environment, preserved from bacterial contamination, decomposition, autolysis, and metabolic reactions. The post-mortem analysis of VH provides an important tool for the estimation of the post-mortem interval (PMI), which can be helpful in determining the cause of death. Consequently, the present review evaluates the recent chemical and biochemical advances with particular importance on the endogenous compounds present at the time of death and their modification over time, which are valuable for the PMI prediction and to identify the cause of death.
Topics: Autopsy; Forensic Pathology; Humans; Illicit Drugs; Postmortem Changes; Vitreous Body
PubMed: 32169668
DOI: 10.1016/j.forsciint.2020.110235 -
Current Opinion in Ophthalmology May 2021Symptomatic vitreous opacities are increasingly recognized as a significant burden to patient well-being. There is growing interest in the use of vitrectomy or laser... (Review)
Review
PURPOSE OF REVIEW
Symptomatic vitreous opacities are increasingly recognized as a significant burden to patient well-being. There is growing interest in the use of vitrectomy or laser treatment to address these problems. This review is intended to update current assessment, management, and risks of treatment for persistent severely symptomatic vitreous opacities.
RECENT FINDINGS
Despite studies showing the value of quantitative ultrasound, reading speed measurements, and contrast sensitivity for assessing dysfunction caused by vitreous opacities, the decision of whether to proceed with surgery remains a very subjective, clinical one. Visual Function Questionnaire-25 score studies show a very large improvement postvitrectomy consistent with relief from symptoms and patient satisfaction. The risk of retinal tear and detachment appears to be higher than in most conditions treated with vitrectomy.
SUMMARY
Vitrectomy for the management of severe vitreous opacities is increasingly accepted because of the tremendous relief of symptoms reported by patients. The risks of retinal tear and detachment remain a concern, particularly in patients who have an attached posterior hyaloid. Yttrium-aluminum-garnet laser treatment of floaters may offer benefit in a subset of patients but appears to be less definitive than vitrectomy, and also may carry significant risk.
Topics: Eye Diseases; Humans; Laser Therapy; Lasers, Solid-State; Vitrectomy; Vitreous Body
PubMed: 33710011
DOI: 10.1097/ICU.0000000000000752 -
Nippon Ganka Gakkai Zasshi Mar 2015The macula is a site where various vitreoretinal disorders occur. In 1983 we started to observe the retinal surface of postmortem eyes with a scanning electron... (Review)
Review
The macula is a site where various vitreoretinal disorders occur. In 1983 we started to observe the retinal surface of postmortem eyes with a scanning electron microscope (SEM). We investigated the anatomy of the vitreous in postmortem eyes by slit lamp biomicroscopy. The novel anatomy of the premacular vitreous led us to conduct a clinical study of vitreomacular interface diseases. In 1997, time domain optical coherence tomography(OCT) became available which facilitated visualization of the vitreoretinal interface. Swept source OCT which was introduced in 2012 can depict liquefied lacunae in the vitreous. It enabled us to elucidate the mechanism of vitreoretinal diseases. I. SEM revealed the remnants of vitreous cortex at fovea with high incidence (44%), which suggests strong vitreoretinal attachment at the fovea and vitreous cortex origin of the epiretinal membrane. II. We studied the anatomy of the vitreous in postmortem eyes. The vitreous of bisected eye balls was stained by fluorescein and immersed in water and observed by slit-lamp biomicroscopy. We discovered a "posterior precortical vitreous pocket (PPVP)" in adult eyes without posterior vitreous detachment (PVD). III. We performed clinical study in various vitreoretinal diseases based on the novel vitreous anatomy and explained their mechanism. 1. In diabetic retinopathy, ring shaped fibrovascular tissue surrounding the macula is formed along the outer margin of the PPVP. Although PVD progresses outside the PPVP, its posterior wall remains attached to the retina, which causes macular traction or cystoid macular edema. 2. In eyes with idiopathic epimacular membrane (IEM), detached vitreous cortex had an oval defect corresponding to the IEM. Posterior wall of the PPVP that is premacular vitreous cortex appeared to be the framework of IEM. 3. During vitrectomy for macular hole, premacular round defect appears when PVD is created. The residual cortex on the macula is fibrous membrane with elasticity. The tangential contraction of premacular cortex may generate anterior traction to the fovea, which leads to macular hole. IV. Using time domain OCT, we demonstrated the evolution of macular hole, myopic foveoschisis and lamellar macular hole. After 2007, we investigated age related changes of vitreoretinal interface by spectral domain OCT V. We demonstrated whole structure of the PPVP using swept source OCT. PPVP is a boat shaped premacular liquefied space which has a connecting channel to Cloquet's canal. PPVP develops during childhood. Visualization of vitreous structure proved that our previous assumptions are reasonable. Although the physiological function of the PPVP is unclear, we speculate that the aqueous flows into the PPVP though Cloquet's canal and the connecting channel.
Topics: Diabetic Retinopathy; Humans; Macula Lutea; Microscopy, Electron; Visual Perception; Vitrectomy; Vitreous Body
PubMed: 25854107
DOI: No ID Found -
Translational Vision Science &... Feb 2023The purpose of this study was to assess the performance of ultrasonic (US) vitrectomy devices by quantifying and comparing its impact on extracted vitreous properties to...
PURPOSE
The purpose of this study was to assess the performance of ultrasonic (US) vitrectomy devices by quantifying and comparing its impact on extracted vitreous properties to conventional pneumatic blade (PB) cutters using micro-extensional rheology. US vitrectomy is a new technology that offers an alternative to PB cutters used in vitreo-retinal surgeries.
METHODS
Thirty-six porcine vitreous samples were extracted using US and PB cutters. Each sample was kept at 4°C and tested within 24 hours postmortem and 4 hours post-vitrectomy. A recently developed micro-extensional rheology technique is used to infer the relative protein fragment size of extracted vitreous by quantifying the extensional relaxation time.
RESULTS
US-extracted vitreous exhibited extensional relaxation times orders of magnitude lower than PB-extracted vitreous (0.37 ms and 27.25 ms, respectively). Relaxation time is directly correlated to the fragment size of the collagen fibers in the vitreous. The formation of beads-on-a-string droplets within the PB samples indicates the presence of larger collagen fragments. These droplets were not seen on US samples.
CONCLUSIONS
This new micro-extensional rheology technique can identify significant differences in physical properties of extracted vitreous. Long relaxation times and beads-on-a-string droplets within the PB vitreous samples indicate larger protein fragments compared to the US samples.
TRANSLATIONAL RELEVANCE
Higher fragmentation of vitreous and lower extensional relaxation times may improve retina safety due to a reduction in vitreo-retinal traction resulting from the continuous shear action and aspiration applied by ultrasonic vitrectomy technology.
Topics: Swine; Animals; Vitrectomy; Vitreous Body; Ultrasonics; Collagen; Rheology
PubMed: 36790819
DOI: 10.1167/tvst.12.2.24 -
Frontiers in Immunology 2023Diabetic retinopathy (DR) and age-related macular degeneration (AMD) are leading causes of visual impairment and blindness in people aged 50 years or older in...
Proteomics profiling of vitreous humor reveals complement and coagulation components, adhesion factors, and neurodegeneration markers as discriminatory biomarkers of vitreoretinal eye diseases.
INTRODUCTION
Diabetic retinopathy (DR) and age-related macular degeneration (AMD) are leading causes of visual impairment and blindness in people aged 50 years or older in middle-income and industrialized countries. Anti-VEGF therapies have improved the management of neovascular AMD (nAMD) and proliferative DR (PDR), no treatment options exist for the highly prevalent dry form of AMD.
METHODS
To unravel the biological processes underlying these pathologies and to find new potential biomarkers, a label-free quantitative (LFQ) method was applied to analyze the vitreous proteome in PDR (n=4), AMD (n=4) compared to idiopathic epiretinal membranes (ERM) (n=4).
RESULTS AND DISCUSSION
Post-hoc tests revealed 96 proteins capable of differentiating among the different groups, whereas 118 proteins were found differentially regulated in PDR compared to ERM and 95 proteins in PDR compared to dry AMD. Pathway analysis indicates that mediators of complement, coagulation cascades and acute phase responses are enriched in PDR vitreous, whilst proteins highly correlated to the extracellular matrix (ECM) organization, platelet degranulation, lysosomal degradation, cell adhesion, and central nervous system development were found underexpressed. According to these results, 35 proteins were selected and monitored by MRM (multiple reaction monitoring) in a larger cohort of patients with ERM (n=21), DR/PDR (n=20), AMD (n=11), and retinal detachment (n=13). Of these, 26 proteins could differentiate between these vitreoretinal diseases. Based on Partial least squares discriminant and multivariate exploratory receiver operating characteristic (ROC) analyses, a panel of 15 discriminatory biomarkers was defined, which includes complement and coagulation components (complement C2 and prothrombin), acute-phase mediators (alpha-1-antichymotrypsin), adhesion molecules (e.g., myocilin, galectin-3-binding protein), ECM components (opticin), and neurodegeneration biomarkers (beta-amyloid, amyloid-like protein 2).
Topics: Humans; Vitreous Body; Angiogenesis Inhibitors; Proteomics; Vascular Endothelial Growth Factor A; Visual Acuity; Wet Macular Degeneration; Complement System Proteins; Biomarkers; Diabetic Retinopathy; Epiretinal Membrane
PubMed: 36875133
DOI: 10.3389/fimmu.2023.1107295 -
International Journal of Molecular... Jul 2021Diabetic retinopathy is one of the leading causes of blindness in the world with the incidence of disease ever-increasing worldwide. The vitreous humor represents an... (Review)
Review
Diabetic retinopathy is one of the leading causes of blindness in the world with the incidence of disease ever-increasing worldwide. The vitreous humor represents an extensive and complex interactive arena for cytokines in the diabetic eye. In recent decades, there has been significant progress in understanding this environment and its implications in disease pathophysiology. In this review, we investigate the vitreous ecosystem in diabetic retinopathy at the molecular level. Areas of concentration include: the current level of knowledge of growth factors, cytokine and chemokine mediators, and lipid-derived metabolites in the vitreous. We discuss the molecular patho-mechanisms of diabetic retinopathy based upon current vitreous research.
Topics: Aqueous Humor; Chemokines; Cytokines; Diabetes Mellitus; Diabetic Retinopathy; Humans; Intercellular Signaling Peptides and Proteins; Interleukins; Vitreous Body
PubMed: 34281192
DOI: 10.3390/ijms22137142 -
Fa Yi Xue Za Zhi Feb 2023Estimation of postmortem interval (PMI) is one of the important research contents in forensic pathology, and it has always been the focus and hot spot of research work.... (Review)
Review
Estimation of postmortem interval (PMI) is one of the important research contents in forensic pathology, and it has always been the focus and hot spot of research work. In recent years, scholars at home and abroad have made some research progress in estimating PMI by using ocular tissue. After death, the changes of cornea, aqueous humor, iris, lens, vitreous humor and retina all show time sequence change rule highly related to PMI. This paper reviews the research progress of PMI estimation based on the morphological, biochemical, molecular and genetic material changes of different ocular tissue structures after death, and discusses the existing problems and development trends.
Topics: Humans; Postmortem Changes; Time Factors; Autopsy; Vitreous Body; Forensic Pathology
PubMed: 37038856
DOI: 10.12116/j.issn.1004-5619.2021.410602 -
Journal of Alzheimer's Disease : JAD 2023Patients with eye disease have an increased risk for developing neurodegenerative disease. Neurodegenerative proteins can be measured in the eye; however, correlations...
BACKGROUND
Patients with eye disease have an increased risk for developing neurodegenerative disease. Neurodegenerative proteins can be measured in the eye; however, correlations between biomarker levels in eye fluid and neuropathological diagnoses have not been established.
OBJECTIVE
This exploratory, retrospective study examined vitreous humor from 41 postmortem eyes and brain tissue with neuropathological diagnoses of Alzheimer's disease (AD, n = 7), chronic traumatic encephalopathy (CTE, n = 15), both AD + CTE (n = 10), and without significant neuropathology (controls, n = 9).
METHODS
Protein biomarkers i.e., amyloid-β (Aβ40,42), total tau (tTau), phosphorylated tau (pTau181,231), neurofilament light chain (NfL), and eotaxin-1 were quantitatively measured by immunoassay. Non-parametric tests were used to compare vitreous biomarker levels between groups. Spearman's rank correlation tests were used to correlate biomarker levels in vitreous and cortical tissue. The level of significance was set to α= 0.10.
RESULTS
In pairwise comparisons, tTau levels were significantly increased in AD and CTE groups versus controls (p = 0.08 for both) as well as AD versus AD+CTE group and CTE versus AD+CTE group (p = 0.049 for both). Vitreous NfL levels were significantly increased in low CTE (Stage I/II) versus no CTE (p = 0.096) and in low CTE versus high CTE stage (p = 0.03). Vitreous and cortical tissue levels of pTau 231 (p = 0.02, r = 0.38) and t-Tau (p = 0.04, r = -0.34) were significantly correlated.
CONCLUSION
The postmortem vitreous humor biomarker levels significantly correlate with AD and CTE pathology in corresponding brains, while vitreous NfL was correlated with the CTE staging. This exploratory study indicates that biomarkers in the vitreous humor may serve as a proxy for neuropathological disease.
Topics: Humans; Alzheimer Disease; Chronic Traumatic Encephalopathy; Neurodegenerative Diseases; Retrospective Studies; Vitreous Body; Brain; tau Proteins; Amyloid beta-Peptides; Biomarkers
PubMed: 37182888
DOI: 10.3233/JAD-230167