Radiotherapy-induced alterations in vitreous humor: A new potential critical structure

Object The authors investigated the use of different collimator values in different sectors (hybrid shots) when treating patients with lesions close to critical structures with the Perfexion model Gamma Knife. Methods Twelve patients with various tumors (6 with a pituitary tumor, 3 with vestibular schwannoma, 2 with meningioma, and 1 with metastatic lesion) that were within 4 mm of the brainstem, optic nerve, pituitary stalk, or cochlea were considered. All patients were treated at the authors' institution between June 2007 and March 2008. The patients' treatments were replanned in 2 different ways. In the first plan, hybrid shots were used such that the steepest dose gradient was aligned with the junction between the target and the critical structure(s). This was accomplished by placing low-value collimators in appropriate sectors. In the second plan, no hybrid shots were used. Sector blocking (either manual or dynamic) was required for all plans to reduce the critical structure doses to acceptable levels. Prescribed doses ranged from 12 to 30 Gy at the periphery of the target. The plans in each pair were designed to be equally conformal in terms of both target coverage (as measured by the Paddick conformity index) and critical structure sparing. Results The average number of shots required was roughly the same using either planning technique (16.7 vs 16.6 shots with and without hybrids). However, for all patients, the number of blocked sectors required to protect critical areas was larger when hybrid shots were not used. On average, nearly twice as many blocked sectors (14.8 vs 7.0) were required for the plans that did not use hybrid shots. The number of high-value collimators used in each plan was also evaluated. For small targets (≤ 1 cm3), for which 8 mm was considered a high value for the collimator, plans employing hybrids used an average of 2.3 times as many 8-mm sectors as did their nonhybrid counterparts (7.4 vs 3.2 sectors). For large targets (> 1 cm3), for which 16 mm was considered a high value for the collimator, hybrid plans used an average of 1.4 times as many 16-mm sectors as did the plans without hybrids (10.7 vs 7.7 sectors). Decreasing the number of blocked sectors and increasing the number of high-value collimator sectors led to use of shorter beam-on times. Beam-on times were 1–39% higher (average 17%) when hybrid shots were not allowed. The average beam-on time for plans with and without hybrid shots was 67.4 versus 78.4 minutes. Conclusions The judicious use of hybrid shots in patients for whom the target is close to a critical structure is an efficient way to achieve conformal treatments while minimizing the beam-on time. The reduction in beam-on time with hybrid shots is attributed to a reduced use of blocked sectors and an increased number of high-value collimator sectors.

Download Full-text

The Molecular Basis of Double-Strand DNA Break Repair: The Critical Structure of the RAD52/RPA Complex

10.21236/ada396587 ◽

2001 ◽

Author(s):

Dobra D. Jackson ◽

Gloria Borgstahl

Keyword(s):

Molecular Basis ◽

Dna Break ◽

Dna Break Repair ◽

Break Repair ◽

Critical Structure ◽

Double Strand Dna

Download Full-text

The Profile of Angiogenic Factors in Vitreous Humor of the Patients with Proliferative Diabetic Retinopathy

Current Molecular Medicine ◽

10.2174/1566524017666171106111440 ◽

2017 ◽

Vol 17 (4) ◽

Cited By ~ 6

Author(s):

Y. Yu ◽

J. Zhang ◽

R. Zhu ◽

R. Zhao ◽

J. Chen ◽

...

Keyword(s):

Diabetic Retinopathy ◽

Proliferative Diabetic Retinopathy ◽

Vitreous Humor ◽

Angiogenic Factors

Download Full-text

Intentional communication and the anterior cingulate cortex

Interaction Studies ◽

10.1075/is.6.2.04ben ◽

2005 ◽

Vol 6 (2) ◽

pp. 201-221 ◽

Cited By ~ 7

Author(s):

Oana Benga

Keyword(s):

Social Cognition ◽

Anterior Cingulate Cortex ◽

Cingulate Cortex ◽

Anterior Cingulate ◽

Neural Structure ◽

Intentional Communication ◽

Attention Skills ◽

Starting Point ◽

Prelinguistic Communication ◽

Critical Structure

This paper presents arguments for considering the anterior cingulate cortex (ACC) as a critical structure in intentional communication. Different facets of intentionality are discussed in relationship to this neural structure. The macrostructural and microstructural characteristics of ACC are proposed to sustain the uniqueness of its architecture, as an overlap region of cognitive, affective and motor components. At the functional level, roles played by this region in communication include social bonding in mammals, control of vocalization in humans, semantic and syntactic processing, and initiation of speech. The involvement of the anterior cingulate cortex in social cognition is suggested where, for infants, joint attention skills are considered both prerequisites of social cognition and prelinguistic communication acts. Since the intentional dimension of gestural communication seems to be connected to a region previously equipped for vocalization, ACC might well be a starting point for linguistic communication.

Download Full-text

Bio-Distribution and Pharmacokinetics of Topically Administered γ-Cyclodextrin Based Eye Drops in Rabbits

Pharmaceuticals ◽

10.3390/ph14050480 ◽

2021 ◽

Vol 14 (5) ◽

pp. 480

Author(s):

Martin Kallab ◽

Kornelia Schuetzenberger ◽

Nikolaus Hommer ◽

Bhavapriya Jasmin Schäfer ◽

Doreen Schmidl ◽

...

Keyword(s):

Single Dose ◽

Drug Concentration ◽

Vitreous Humor ◽

Controlled Study ◽

Eye Drops ◽

Corneal Tissue ◽

Single Administration ◽

Local Tolerability ◽

Dose Administration ◽

Retinal Tissue

The purpose of this study was to evaluate the ocular pharmacokinetics, bio-distribution and local tolerability of γ-cyclodextrin (γCD) based irbesartan 1.5% eye drops and candesartan 0.15% eye drops after single and multiple topical administration in rabbit eyes. In this randomized, controlled study, a total number of 59 New Zealand White albino rabbits were consecutively assigned to two study groups. Group 1 (n = 31) received irbesartan 1.5% and group 2 (n = 28) candesartan 0.15% eye drops. In both groups, single dose and multiple administration pharmacokinetic studies were performed. Rabbits were euthanized at five predefined time points after single-dose administration, whereas multiple-dose animals were dosed for 5 days twice-daily and then euthanized 1 h after the last dose administration. Drug concentration was measured by using liquid chromatography-tandem mass spectrometry (LC-MS/MS) in the retinal tissue, vitreous humor, aqueous humor, corneal tissue and in venous blood samples. Pharmacokinetic parameters including maximal drug concentration (Cmax), time of maximal drug concentration (Tmax), half-life and AUC were calculated. To assess local tolerability, six additional rabbits received 1.5% irbesartan eye drops twice daily in one eye for 28 days. Tolerability was assessed using a modified Draize test and corneal sensibility by Cochet Bonnet esthesiometry. Both γCD based eye drops were rapidly absorbed and distributed in the anterior and posterior ocular tissues. Within 0.5 h after single administration, the Cmax of irbesartan and candesartan in retinal tissue was 251 ± 142 ng/g and 63 ± 39 ng/g, respectively. In the vitreous humor, a Cmax of 14 ± 16 ng/g for irbesartan was reached 0.5 h after instillation while Cmax was below 2 ng/g for candesartan. For multiple dosing, the observed Cmean in retinal tissue was 338 ± 124 ng/g for irbesartan and 36 ± 10 ng/g for candesartan, whereas mean vitreous humor concentrations were 13 ± 5 ng/g and <2 ng/g, respectively. The highest plasma concentrations of both irbesartan (Cmax 5.64 ± 4.08 ng/mL) and candesartan (Cmax 4.32 ± 1.04 ng/mL) were reached 0.5 h (Tmax) after single administration. Local tolerability was favorable with no remarkable differences between the treated and the control eyes. These results indicate that irbesartan and candesartan in γCD based nanoparticle eye drops can be delivered to the retinal tissue of the rabbit’s eye in pharmacologically relevant concentrations. Moreover, safety and tolerability profiles appear to be favorable in the rabbit animal model.

Download Full-text

Application of Innovative TGA/Chemometric Approach for Forensic Purposes: The Estimation of the Time since Death in Contaminated Specimens

Diagnostics ◽

10.3390/diagnostics11010121 ◽

2021 ◽

Vol 11 (1) ◽

pp. 121

Author(s):

Roberta Risoluti ◽

Giuseppina Gullifa ◽

Vittorio Fineschi ◽

Paola Frati ◽

Stefano Materazzi

Keyword(s):

Multidisciplinary Approach ◽

Vitreous Humor ◽

Classification Model ◽

Forensic Sciences ◽

Time Since Death ◽

Time Of Death ◽

Novel Approach ◽

Chemometric Approach ◽

Postmortem Examinations

Chronothanatology has always been a challenge in forensic sciences. Therefore, the importance of a multidisciplinary approach for the characterization of matrices (organs, tissues, or fluids) that respond linearly to the postmortem interval (PMI) is emerging increasingly. The vitreous humor is particularly suitable for studies aimed at assessing time-related modifications because it is topographically isolated and well-protected. In this work, a novel approach based on thermogravimetry and chemometrics was used to estimate the time since death in the vitreous humor and to collect a databank of samples derived from postmortem examinations after medico–legal evaluation. In this study, contaminated and uncontaminated specimens with tissue fragments were included in order to develop a classification model to predict time of death based on partial least squares discriminant analysis (PLS-DA) that was as robust as possible. Results demonstrate the possibility to correctly predict the PMI even in contaminated samples, with an accuracy not lower than 70%. In addition, the correlation coefficient of the measured versus predicted outcomes was found to be 0.9978, confirming the ability of the model to extend its feasibility even to such situations involving contaminated vitreous humor.

Download Full-text

Spectroscopy as a useful tool for the identification of changes with time in post-mortem vitreous humor for forensic toxicology purposes

Monatshefte für Chemie - Chemical Monthly ◽

10.1007/s00706-021-02786-8 ◽

2021 ◽

Author(s):

Anna Wójtowicz ◽

Agata Mitura ◽

Renata Wietecha-Posłuszny ◽

Rafał Kurczab ◽

Marcin Zawadzki

Keyword(s):

Ir Spectra ◽

Forensic Toxicology ◽

Principal Component ◽

Hierarchical Cluster ◽

Vitreous Humor ◽

Attenuated Total Reflection ◽

Glass Slides ◽

Added Benefit ◽

Ft Ir ◽

Non Destructive

AbstractVitreous humor (VH) is an alternative biological matrix with a great advantage of longer availability for analysis due to the lack of many enzymes. The use of VH in forensic toxicology may have an added benefit, however, this application requires rapid, simple, non-destructive, and relatively portable analytical analysis methods. These requirements may be met by Fourier transform infrared spectroscopy technique (FT-IR) equipped with attenuated total reflection accessory (ATR). FT-IR spectra of vitreous humor samples, deposited on glass slides, were collected and subsequent chemometric data analysis by means of Hierarchical Cluster Analysis and Principal Component Analysis was conducted. Differences between animal and human VH samples and human VH samples stored for diverse periods of time were detected. A kinetic study of changes in the VH composition up to 2 weeks showed the distinction of FT-IR spectra collected on the 1st and 14th day of storage. In addition, data obtained for the most recent human vitreous humor samples—collected 3 and 2 years before the study, presented successful discrimination of all time points studied. The method introduced was unable to detect mephedrone addition to VH in the concentration of 10 µg/cm3. Graphic abstract

Download Full-text

Enhanced Transport and Permeation of a Polymeric Nanocarrier across the Retina by Mixing with ATP upon Intravitreal Injection

Pharmaceutics ◽

10.3390/pharmaceutics13040463 ◽

2021 ◽

Vol 13 (4) ◽

pp. 463

Author(s):

Kiyoon Kwon ◽

Youngmin Hwang ◽

Junyoung Jung ◽

Giyoong Tae

Keyword(s):

Great Increase ◽

Pigment Epithelium ◽

Outer Part ◽

Vitreous Humor ◽

Retinal Diseases ◽

P2y Receptor ◽

Main Site ◽

Tight Junction Disruption ◽

Polymeric Nanocarrier ◽

Retina Pigment Epithelium

The outer part of the retina pigment epithelium (RPE) in the retina is the main site of neovascularization associated with retinal diseases. However, various obstacles interrupt the delivery of medicines across the RPE, mainly due to the well-developed tight junctions in the RPE. Currently, there is no practical formulation to overcome this issue. In this study, we demonstrated that simple mixing with adenosine tetraphosphate (ATP) has the potential to greatly enhance the transport and permeation of a polymeric nanocarrier across the retina via intravitreal administration. Chitosan-functionalized, pluronic-based nanocarrier (NC), which can deliver various biomolecules efficiently, was used as a polymeric nanocarrier. Mixing with ATP facilitated the diffusion of the nanocarrier in the vitreous humor by reducing the electrostatic interaction between NC and negatively charged glycosaminoglycans (GAGs) in the vitreous humor. Mixing with ATP also allowed the penetration of NC across the whole retina, and it resulted in a great increase (approximately nine times) in the transport of NC across the retina, as well as spreading it throughout the whole retina upon intravitreal administration in a mouse model. This enhanced permeation across the retina was specific to ATP but not to GTP, suggesting the possibility of P2Y receptor-mediated tight junction disruption by ATP.

Download Full-text

Radiation Absorbed Dose to the Basal Ganglia from Dopamine Transporter Radioligand18F-FPCIT

BioMed Research International ◽

10.1155/2014/498072 ◽

2014 ◽

Vol 2014 ◽

pp. 1-5

Author(s):

William Robeson ◽

Vijay Dhawan ◽

Yilong Ma ◽

David Bjelke ◽

Claude Margouleff ◽

...

Keyword(s):

Basal Ganglia ◽

Dopamine Transporter ◽

Absorbed Dose ◽

Normal Subjects ◽

Residence Times ◽

Time Activity ◽

High Affinity ◽

Critical Organ ◽

Left And Right ◽

Critical Structure

Our previous dosimetry studies have demonstrated that for dopaminergic radiotracers,18F-FDOPA and18F-FPCIT, the urinary bladder is the critical organ. As these tracers accumulate in the basal ganglia (BG) with high affinity and long residence times, radiation dose to the BG may become significant, especially in normal control subjects. We have performed dynamic PET measurements using18F-FPCIT in 16 normal adult subjects to determine if in fact the BG, although not a whole organ, but a well-defined substructure, receives the highest dose. Regions of interest were drawn over left and right BG structures. Resultant time-activity curves were generated and used to determine residence times for dosimetry calculations.S-factors were computed using the MIRDOSE3 nodule model for each caudate and putamen. For18F-FPCIT, BG dose ranged from 0.029 to 0.069 mGy/MBq. In half of all subjects, BG dose exceeded 85% of the published critical organ (bladder) dose, and in three of those, the BG dose exceeded that for the bladder. The BG can become the dose-limiting organ in studies using dopamine transporter ligands. For some normal subjects studied with F-18 or long half-life radionuclide, the BG may exceed bladder dose and become the critical structure.

Download Full-text