scholarly journals Keratoconus: cross-linking the window of the eye

2021 ◽  
Vol 2 ◽  
pp. 263300402110035
Author(s):  
Sally Hayes ◽  
Siân R. Morgan ◽  
Keith M. Meek
Keyword(s):  
Treatment Time ◽  
Standard Procedure ◽  
Clinical Effectiveness ◽  
Patient Comfort ◽  
Patient Treatment ◽  
Cross Linking ◽  
Corneal Transplant ◽  
Eye Drops ◽  
Plain Language ◽  
Cross Links

Keratoconus is a condition in which the cornea progressively thins and weakens, leading to severe, irregular astigmatism and a significant reduction in quality of life. Although the precise cause of keratoconus is still not known, biochemical and structural studies indicate that overactive enzymes within the cornea break down the constituent proteins (collagen and proteoglycans) and cause the tissue to weaken. As the disease develops, collagen fibres slip past each other and are redistributed across the cornea, causing it to change shape. In recent years, it was discovered that the photochemical induction of cross-links within the corneal extracellular matrix, through the use of riboflavin and ultraviolet (UVA) light, could increase the strength and enzymatic resistance of the tissue and thereby halt keratoconus progression. Worldwide acceptance and use of riboflavin/UVA corneal cross-linking therapy for halting keratoconus progression has increased rapidly, in accordance with the growing body of evidence supporting its long-term effectiveness. This review focusses on the inception of riboflavin/UVA corneal cross-linking therapy for keratoconus, its clinical effectiveness and the latest scientific advances aimed at reducing patient treatment time, improving patient comfort and increasing patient eligibility for treatment. Plain language summary Review of current treatments using cross-linking to halt the progress of keratoconus Keratoconus is a disease in which the curved cornea, the transparent window at the front of the eye, weakens, bulges forward into a cone-shape and becomes thinner. This change of curvature means that light is not focussed onto the retina correctly and vision is progressively impaired. Traditionally, the effects of early keratoconus were alleviated by using glasses, specialist contact lenses, rings inserted into the cornea and in severe cases, by performing a corneal transplant. However, it was discovered that by inducing chemical bonds called cross-links within the cornea, the tissue could be strengthened and further thinning and shape changes prevented. The standard cross-linking procedure takes over an hour to perform and involves the removal of the cells at the front of the cornea, followed by the application of Vitamin B2 eye drops and low energy ultraviolet light (UVA) to create new cross-links within the tissue. Clinical trials have shown this standard procedure to be safe and effective at halting keratoconus progression. However, there are many treatment modifications currently under investigation that aim to reduce patient treatment time and increase comfort, such as accelerated cross-linking procedures and protocols that do not require removal of the surface cells. This review describes the different techniques being developed to carry out corneal cross-linking efficiently and painlessly, to halt keratoconus progression and avoid the need for expensive surgery.

A randomized crossover study evaluating two immobilization devices for prostate cancer treatment

2008 ◽  
Vol 7 (3) ◽  
pp. 141-149 ◽  
Author(s):  
T. Sexton ◽  
G. Rodrigues ◽  
G. Bauman ◽  
J. Harriman-Duke ◽  
T. Kron ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Crossover Study ◽  
Random Error ◽  
Treatment Time ◽  
Ease Of Use ◽  
Patient Comfort ◽  
Patient Treatment ◽  
Random Errors ◽  
Prostate Radiotherapy ◽  
Immobilization Device

AbstractPurpose: To compare the Combifix® immobilization device with a conventional double-leg cushion in terms of patient comfort, therapist feedback and systematic/random error outcomes.Materials and Methods: This prospective block-randomised crossover study enrolled 18 high-risk prostate cancer patients who received whole pelvic plus prostate radiotherapy. Treatment consisted of a prostate boost with one immobilization device followed by whole pelvic radiation using the other device. Our primary endpoints were device ease-of-use and patient comfort. Secondary endpoints included treatment time and systematic/random error assessments.Results: While our patients found both devices equally comfortable and easy to use, the therapists preferred the leg cushion for ease of set-up (p = 0.04). Patient treatment time was similar for the two devices. In terms of electronic portal imaging (EPID)-based isocentre shifts, statistically, but not clinically, significant differences in systematic and random errors between the two devices exist in the superior–inferior directions (p ≤ 0.05).Conclusions: No clinically important advantage was seen with the Combifix® device versus our standard double-leg cushion in terms of patient/therapist preference, patient comfort, and bony pelvic immobilization. However, this research project confirmed the feasibility of mounting a small single-institution randomised crossover technology assessment related to a practical radiotherapy issue.

scholarly journals Chemistry of collagen cross-links: glucose-mediated covalent cross-linking of type-IV collagen in lens capsules

1993 ◽  
Vol 296 (2) ◽  
pp. 489-496 ◽  
Author(s):  
A J Bailey ◽  
T J Sims ◽  
N C Avery ◽  
C A Miles
Keyword(s):  
Type Iv Collagen ◽  
Cross Linking ◽  
Mechanical And Thermal Properties ◽  
Maximum Strain ◽  
Scanning Calorimetry ◽  
Melting Temperatures ◽  
Type Iv ◽  
Collagen Molecules ◽  
Cross Links

The incubation of lens capsules with glucose in vitro resulted in changes in the mechanical and thermal properties of type-IV collagen consistent with increased cross-linking. Differential scanning calorimetry (d.s.c.) of fresh lens capsules showed two major peaks at melting temperatures Tm 1 and Tm 2 at approx. 54 degrees C and 90 degrees C, which can be attributed to the denaturation of the triple helix and 7S domains respectively. Glycosylation of lens capsules in vitro for 24 weeks caused an increase in Tm 1 from 54 degrees C to 61 degrees C, while non-glycosylated, control incubated capsules increased to a Tm 1 of 57 degrees C. The higher temperature required to denature the type-IV collagen after incubation in vitro suggested increased intermolecular cross-linking. Glycosylated lens capsules were more brittle than fresh samples, breaking at a maximum strain of 36.8 +/- 1.8% compared with 75.6 +/- 6.3% for the fresh samples. The stress at maximum strain (or ‘strength’) was dramatically reduced from 12.0 to 4.7 N.mm.mg-1 after glycosylation in vitro. The increased constraints within the system leading to loss of strength and increased brittleness suggested not only the presence of more cross-links but a difference in the location of these cross-links compared with the natural lysyl-aldehyde-derived cross-links. The chemical nature of the fluorescent glucose-derived cross-link following glycosylation was determined as pentosidine, at a concentration of 1 pentosidine molecule per 600 collagen molecules after 24 weeks incubation. Pentosidine was also determined in the lens capsules obtained from uncontrolled diabetics at a level of about 1 per 100 collagen molecules. The concentration of these pentosidine cross-links is far too small to account for the observed changes in the thermal and mechanical properties following incubation in vitro, clearly indicating that another as yet undefined, but apparently more important cross-linking mechanism mediated by glucose is taking place.

scholarly journals Cross-linking of the electron-transfer flavoprotein to electron-transfer flavoprotein-ubiquinone oxidoreductase with heterobifunctional reagents

1988 ◽  
Vol 255 (3) ◽  
pp. 869-876 ◽  
Author(s):  
D J Steenkamp
Keyword(s):  
Electron Transfer ◽  
Small Subunit ◽  
Cross Linking ◽  
Minor Effect ◽  
Electron Transfer Flavoprotein ◽  
Ubiquinone Oxidoreductase ◽  
Lysine Residues ◽  
Cross Links ◽  
A Minor ◽  
Chemical Cross Linking

The mitochondrial electron-transfer flavoprotein (ETF) is a heterodimer containing only one FAD. In previous work on the structure-function relationships of ETF, its interaction with the general acyl-CoA dehydrogenase (GAD) was studied by chemical cross-linking with heterobifunctional reagents [D. J. Steenkamp (1987) Biochem. J. 243, 519-524]. GAD whose lysine residues were substituted with 3-(2-pyridyldithio)propionyl groups was preferentially cross-linked to the small subunit of ETF, the lysine residues of which had been substituted with 4-mercaptobutyramidine (MBA) groups. This work was extended to the interaction of ETF with ETF-ubiquinone oxidoreductase (ETF-Q ox). ETF-Q ox was partially inactivated by modification with N-succinimidyl 3-(2-pyridyldithio)propionate to introduce pyridyl disulphide structures. A similar modification of ETF caused a large increase in the apparent Michaelis constant of ETF-Q ox for modified ETF owing to the loss of positive charge on some critical lysines of ETF. When ETF-Q ox was modified with 2-iminothiolane to introduce 4-mercaptobutyramidine groups, only a minor effect on the activity of the enzyme was observed. To retain the positive charges on the lysine residues of ETF, pyridyl disulphide structures were introduced by treating ETF with 2-iminothiolane in the presence of 2,2′-dithiodipyridyl. The electron-transfer activity of the resultant ETF preparation containing 4-(2-pyridyldithio)butyramidine (PDBA) groups was only slightly affected. When ETF-Q ox substituted with MBA groups was mixed with ETF bearing PDBA groups, at least 70% of the cross-links formed between the two proteins were between the small subunit of ETF and ETF-Q ox. ETF-Q ox, therefore, interacts predominantly with the same subunit of ETF as GAD. Variables which affect the selectivity of ETF-Q ox cross-linking to the subunits of ETF are considered.

scholarly journals Native cross-links in collagen fibrils induce resistance to human synovial collagenase

1979 ◽  
Vol 181 (3) ◽  
pp. 639-645 ◽  
Author(s):  
C A Vater ◽  
E D Harris ◽  
R C Siegel
Keyword(s):  
Lysyl Oxidase ◽  
Collagen Fibrils ◽  
Bone Collagen ◽  
Collagen Molecule ◽  
Cross Linking ◽  
Pathological Conditions ◽  
Insoluble Material ◽  
Induce Resistance ◽  
Cross Links

A model system consisting of highly purified lysyl oxidase and reconstituted lathyritic chick bone collagen fibrils was used to study the effect of collagen cross-linking on collagen degradation by mammalian collagenase. The results indicate that synthesis of approx. 0.1 Schiff-base cross-link per collagen molecule results in a 2–3-fold resistance to human synovial collagenase when compared with un-cross-linked controls or samples incubated in the presence of beta-aminopropionitrile to inhibit cross-linking. These results confirm previous studies utilizing artificially cross-linked collagens, or collagens isolated as insoluble material after cross-linking in vivo, and suggest that increased resistance to collagenase may be one of the earliest effects of cross-linking in vivo. The extent of intermolecular cross-linking among collagen fibrils may provide a mechanism for regulating the rate of collagen catabolism relative to synthesis in normal and pathological conditions.

EXPERIMENTAL VALIDATION OF THE CHARLESBY AND HORIKX MODELS APPLIED TO DE-VULCANIZATION OF SULFUR AND PEROXIDE VULCANIZATES OF NR AND EPDM

2016 ◽  
Vol 89 (4) ◽  
pp. 671-688 ◽  
Author(s):  
M. A. L. Verbruggen ◽  
L. van der Does ◽  
W. K. Dierkes ◽  
J. W. M. Noordermeer
Keyword(s):  
Experimental Validation ◽  
Main Chain ◽  
Sol Gel ◽  
Chain Scission ◽  
Cross Linking ◽  
Cross Link ◽  
Practical Reality ◽  
Cross Links ◽  
The Cross ◽  
Theoretical Considerations

ABSTRACT The theoretical model developed by Charlesby to quantify the balance between cross-links creation of polymers and chain scission during radiation cross-linking and further modifications by Horikx to describe network breakdown from aging were merged to characterize the balance of both types of scission on the development of the sol content during de-vulcanization of rubber networks. There are, however, disturbing factors in these theoretical considerations vis-à-vis practical reality. Sulfur- and peroxide-cured NR and EPDM vulcanizates were de-vulcanized under conditions of selective cross-link and random main-chain scissions. Cross-link scission was obtained using thiol-amine reagents for selective cleavage of sulfur cross-links. Random main-chain scission was achieved by heating peroxide vulcanizates of NR with diphenyldisulfide, a method commonly employed for NR reclaiming. An important factor in the analyses of these experiments is the cross-linking index. Its value must be calculated using the sol fraction of the cross-linked network before de-vulcanization to obtain reliable results. The values for the cross-linking index calculated with sol-gel data before de-vulcanization appear to fit the experimentally determined modes of network scission during de-vulcanization very well. This study confirms that the treatment of de-vulcanization data with the merged Charlesby and Horikx models can be used satisfactorily to characterize the de-vulcanization of NR and EPDM vulcanizates.

scholarly journals Localization of the Transglutaminase Cross-Linking Sites in the Bacillus subtilis Spore Coat Protein GerQ

2006 ◽  
Vol 188 (21) ◽  
pp. 7609-7616 ◽  
Author(s):  
Alicia Monroe ◽  
Peter Setlow
Keyword(s):  
Bacillus Subtilis ◽  
Coat Protein ◽  
Cross Linking ◽  
Spore Coat ◽  
Bacillus Subtilis Spore ◽  
Binding Partners ◽  
Lysine Residues ◽  
Cross Links ◽  
Hydrolysis Of ◽  
Spore Coat Protein

ABSTRACT The Bacillus subtilis spore coat protein GerQ is necessary for the proper localization of CwlJ, an enzyme important in the hydrolysis of the peptidoglycan cortex during spore germination. GerQ is cross-linked into high-molecular-mass complexes in the spore coat late in sporulation, and this cross-linking is largely due to a transglutaminase. This enzyme forms an ε-(γ-glutamyl) lysine isopeptide bond between a lysine donor from one protein and a glutamine acceptor from another protein. In the current work, we have identified the residues in GerQ that are essential for transglutaminase-mediated cross-linking. We show that GerQ is a lysine donor and that any one of three lysine residues near the amino terminus of the protein (K2, K4, or K5) is necessary to form cross-links with binding partners in the spore coat. This leads to the conclusion that all Tgl-dependent GerQ cross-linking takes place via these three lysine residues. However, while the presence of any of these three lysine residues is essential for GerQ cross-linking, they are not essential for the function of GerQ in CwlJ localization.

scholarly journals Bound (“Glassy”) Rubber as a Free Radical Cross-linked Rubber Layer on a Carbon Black

Materials ◽  
2018 ◽  
Vol 11 (10) ◽  
pp. 1992 ◽  
Author(s):  
Alexey Kondyurin ◽  
Anastasia Eliseeva ◽  
Alexander Svistkov
Keyword(s):  
Free Radical ◽  
Carbon Black ◽  
Ion Beam ◽  
Cross Linking ◽  
Carbon Filler ◽  
Free Radical Reactions ◽  
Rubber Layer ◽  
Ion Beam Implantation ◽  
Cross Links ◽  
The Cross

A model of rubber with a cross-linked rubber layer on a carbon black filler has been proposed. The cross-links are the result of free radical reactions generated by carbon atoms with unpaired electrons at the edge of graphitic sheets in a carbon black filler. The experimental study of the cross-linking reactions in polyisoprene was done on a flat carbonized surface after ion beam implantation. The cross-linking process in the polyisoprene macromolecules between two particles was simulated. The model with a cross-linked rubber layer on a carbon filler as a “glassy layer” explains the mechanical properties of the rubber materials.

Sign in / Sign up

Export Citation Format

Share Document