photodynamic therapy: shedding light on restenosis

by:EME LIGHTING     2020-03-18
Photodynamic therapy involves the interaction of light-sensitive drugs, light and tissue oxygen 9 (fig 1).
Light sensitizers, many of which are ligand or chemicals with similar structure, can be given locally or systematically.
At the treatment concentration, most photosensitive devices do not have identifiable effects in isolation, and light needs to be applied locally at a wavelength that matches the absorption properties of the photosensitive device.
The sensitive light transfer time is critical for achieving the desired biological response and changes with the drug generation dynamics of individual sensitive individuals. Light—
Usually in the form of red light emitted by a laser-
In order to avoid the power delivery of one of the features of early laser vascular shaping.
When activated by light, the photosensitive device is converted into an electronic excited state, which can transfer energy to tissue oxygen to produce mono-State oxygen, or to other biological molecules to produce other free radical intermediates.
A short half life (0. 6u2009×u200910−6 s)
Diffusion distance (0. 1u2009μm)
The presence of mono-oxygen and other active species means that cell effects are highly confined to where these species produce.
10 activation of photosensitive substances bound to the cell membrane can lead to swelling, bubble formation and shedding of the SAC bubble and inhibit membrane transport systems such as Na/K-ATPase.
Other affected sites include the mitochondrial, Gorky, coarse-sided mesh, and dissolved body.
Toxicity is mediated at the cellular and subcellular levels and may occur through apoptosis or necrosis.
In vitro data confirm PDT-induced apoptosis of human venous endothelial cells in culture
An effect mediated by the release of pigment cells and the activation of semi-enzymes.
Similarly, the main toxic mechanism of PDT for cultured vascular endothelial cells is apoptosis.
The in vivo evidence of apoptosis is discussed below.
Download the action mechanism of figure open figure 1 photo Dynamics therapy in the new tabDownload powerpoint.
The light sensitivity agent is activated by light of a specific wavelength.
In its state of excitement, the photo-sensitive device reacts with tissue oxygen to produce a variety of reactive oxide species, inducing specific cell and extracellular effects, thereby inhibiting re-stenosis (see text).
When the photosensitive device is attenuated back to its ground state, the emission of fluorescence can be used to study the tissue distribution of the sensor.
Most photosensitive cells were excluded from the nucleus, and while small DNA breaks were reported after PDT, DNA damage did not appear to be a major feature and the risk of mutation was low.
This is one of the main benefits of using red light, and the photon energy of red light is too low compared to ultraviolet rays, light in X-rays, and does not cause DNA damage, or, is the gamma ray part of the spectrum. googletag. {});
Most of PDT\'s work so far has been in the oncology area.
Sodium porfcinate with light sensitive agent (Photofrin)
PDT has been approved in the United States to alleviate blocked esophageal tumors (
When all other treatments fail)
For lung cancer that cannot be operated in the early stage.
Several other light sensitizers are at an advanced stage in a series of malignant and malignant prestates of the skin and internal organs and in some non-malignant clinical trials
Age-related diseases such as amd.
People have been interested in PDT and arterial disease since the 1980 s, but, only in the last few years, careful experiments have shown that this treatment may have the biological effects needed to prevent re-stenosis, without unacceptable side effects.
These experiments investigated the role of the greasy muscle and endothelial cells cultured in vitro and their relationship with the extracellular matrix, the uptake and distribution of photosensitive cells in the wall of the artery, and the effect of PDT on normal arteries, light sensitivity of experimental arterial porridge and the effect of PDT on the arterial wall after injury.
In vitro experimental observations show that PDT of the extracellular matrix can lead to a decrease in adhesion, proliferation and migration of greasy smooth muscle cells.
In contrast, induction of endothelial cell migration and proliferation was observed after PDT.
In vitro inhibition of the role of the extracellular matrix alkaline Fibrocell growth factor can lead to a decrease in the proliferation of smooth muscle cells, which reflects the inactivation of growth factors rather than the degeneration of growth factor binding sites.
Similarly, PDT of smooth muscle cells acting together with it
Culture with platelet-derived growth factors can lead to a decrease in collagen production in smooth muscle cells, which may be important to limit the fiber healing response after balloon injury.
In addition, PDT has been shown to increase the cross-junction of collagen in the extracellular matrix, thus creating barriers to the migration of muscle cells.
Some people believe that the inactivation of transforming growth factor beta (TGF β)
At least to a certain extent, PDT is the cause of the rapid growth of endothelial cells observed in animal models within two weeks after PDT.
These specific effects of PDT on smooth muscle and endothelial cells and related cell regulators provide important insights into the use of this technique to inhibit endometrial hyperplasia.
The tissue uptake of the photosensitive device the first photosensitive device applied to the artery is porfsodium (Photofrin)
This was done on autopsy tissue.
Recent work in the body has paid special attention to aluminum salt phthalocyanine elite (AlSPc), 5-
Amino ketone acid (5-ALA)
And Texas. 20-22 5-
ALA is not a photosensitive person in itself.
It is an endogenous precursor in the process of haem Biological synthesis, which is converted into photoactive metabolites original or protein IX in vivo. 5-
Production of ALA is usually limited by the haem feedback loop, but if an excess of exogenous 5-
ALA has an accumulation of the original hair protein IX because the latter is eventually converted into haem and then becomes a speed limit step for haem synthesis.
23 Most light sensitizers emit fluorescence, so their distribution in tissues can be studied by fluorescence microscopy of biopsy at different times after administration.
After whole-body administration, both AlSPc and protangin IX showed dose-and time-dependent uptake of the arterial wall endometrium, middle layer, and off-membrane. 2021 5-
At present, ALA has aroused special interest.
Experiments have shown that, 4-6 hours after intravenous administration, there is a high concentration of the original alpha protein IX in the pig arterial medium, 21 and the effect of PDT can be limited to the arterial wall, no impact on other neighboring organizations.
The drug can be administered through the mouth, and the skin light sensitive time is limited to 24-48 hours.
At a clinical dose of 60 mg/kg, 24 side effects were minimal, although they did include a brief increase in mild nausea and liver transferases.
Protoporphyrin IX has a convenient absorption peak at 635 nm in the red part of the visible spectrum.
Using a variety of drug delivery systems, including porous and pipeline balloons and needle injection tubes, several researchers explored the concept of local delivery of light-sensitive devices to arterial walls.
222526 this concept is attractive, but although local absorption can be achieved, given that it is difficult to achieve uniform sensitivity in areas of interest, these photosensitive delivery technologies have little to do with system management
The biological effects of pdt on the normal arterial wall in normal rats and pig arterial walls have caused a unique biological response, the most significant feature of which is the dose-dependent elimination of endothelial stripping and 202127 of medial smooth muscle cells (fig 2).
Perhaps one of the most interesting features is that these histological changes occur in the absence of a local inflammatory response, are evident within three days of treatment and have nothing to do with the sensitivity agent used.
This observation suggests that apoptosis may be the main mechanism of cell damage in vivo.
Recently, the technology used is
TdT-mediated dUDP-biotin 3′-
Oh, Nick\'s end tag)
Transmission electron microscopy and DNA fragments, LaMuraglia and his colleagues have shown that, the loss of new endometrium and medial cells observed after PDT in the common cervical artery of rats with endometrial hyperplasia is limited by this effect to the field of PDT treatment.
28 download the new tabDownload powerpointFigure monthly micro-photo (
X 400 magnification)
Sumu sperm and ihong stained sections of the coronary artery of the pig.
Histological changes observed three days after photodynamic therapy (PDT)(top)
Including endothelial stripping and clearance of medial smooth muscle cells.
The PDT system involves local illumination (
50 J/cm 2 with a wavelength of 635 nm from a copper vapor dye laser)
, 4-6 hours after systemic allergy using an improved standard vascular forming catheter, 5-
Amino ketone acid (ALA).
Comparison of ships showing normal unprocessed (bottom).
However, these predictable and rapid histological changes in the blood vessels are reversible. Re-
It is reported that the inner surface of rats and pigs is completed within 14 days.
2127 in vitro studies of bovine vascular endothelial cells showed that the proliferation of vascular endothelial cells increased after PDT, which may be the result of the loss of activity of transforming growth factor beta.
1529 rapid regeneration of endothelial cells is in contrast to findings after close-range radiation therapy, in which persistent loss of endothelial cells is the cause of late thrombosis occlusion.
8 compared with the rapid recovery of the endothelial surface, the medial reaggregation of smooth muscle cells was delayed after PDT.
PDT was performed on normal rat arteries using 5-5
ALA may result in exhaustion of medial smooth muscle cells for up to six months.
27 despite this significant change in normal cell structure, these changes are not associated with thrombosis, bleeding, or aneuraslike expansion.
2021 however, an obvious problem with loss of medial smooth muscle cells after PDT is that this will have an impact on the structural integrity of the vessel wall.
It is reassuring to observe that there does not appear to be significant changes in the collagen and elastic protein components of the vessel wall after PDT.
30 In addition, Grant and his colleagues showed in the rabbit model of the artery that the mechanical properties of the blood vessels after PDT31 were not affected;
Month using sensitisers-
ALA and AlSPc, the arteries treated with PDT have a higher pressure on the Lumen static hydraulic rupture than the untreated control vessels.
This explanation may be related to the discovery of increased cross-junction of collagen after PDT.
Illumins and his colleagues were light-sensitive and PDT to experimental arterial plaque 1983 and showed that experimental arterial plaque in the aorta of rabbits and Patas monkeys selectively absorbed blood pore protein derivatives.
This sensitivity of as has been confirmed in other experimental models and in human as specimens obtained at autopsy, using other porphyrin derivatives as sensitivity agents.
3233 recently, it has been shown that the interaction of benporto derivatives with low-density lipids enhances the accumulation of this sensitive substance in rabbit as model plaques.
34 water-soluble sensitivity agents, such as the new reagent motexafin lutifen, can be combined with circulating lipids to form a low-density lipid sensitivity agent complex in plasma to promote the treatment of arterial porridge
22. After observing the light sensitivity of the plaque, it was reported that the plaque subsided when the experimental plaque of the rabbit artery was exposed to light.
3536 the results of an experimental arterial atheroma model induced by balloon damage and high cholesterol diet in the coronary arteries of Yucatan mini wine are not very encouraging, only 7 of the 12 arteries treated with Photofrin PDT improved angiography stenosis.
In 1996, Hayashi and his colleague\'s work revealed changes in lipid chemistry after cholesterol PDT and depletion of cholesterol ester, thus providing some insight into the mechanism of plaque fading
There are abundant patches on rabbits.
38 Motexafin GmbH (Lu-
Antlin injection)
Localization in as-plaque-induced macrophages has recently demonstrated that exposure to light in a rabbit model of high-cholesterol levels can reduce plaque quality and the number of arterial wall macrophages.
This may limit the inflammation associated with macrophages, which is a key factor in determining the stability of the plaque.
PDT and response to damaged vessel walls dartsch and associates indicate that incubation with porfcinate and exposure to ultraviolet rays can kill narrow and re-narrow lesions from human Arterial resection specimens
39. These important observations of cells partially responsible for the development of endometrial hyperplasia paved the way for a series of experimental studies on the effects of PDT on animal models after balloon damage in size.
A small animal study by 1992 Ortu and colleagues reported a decrease in endometrial hyperplasia after PDT in balloon-damaged rat common cervical artery.
30 with the use of the sensitivity agent, chloral sulfate phthalocyanine, the light is transmitted to the outer surface of the blood vessel two days or seven days after the injury.
All ships were harvested 14 days after the initial injury.
Other groups also reported a decrease in endometrial hyperplasia in rabbits and rats at different time points after initial arterial balloon injury.
The decrease in endometrial hyperplasia after 4041 PDT was associated with endothelial stripping, depletion of medial cells, reduction of vascular external muscle fibroid cells, and a significant absence of inflammatory response.
Similar to the healing of uninjured arteries after PDT.
The re-aggregation of medial smooth brain cells was delayed compared to rapid restoration of endothelial integrity.
2741 these early studies focused on the effect of PDT on the development or establishment of endometrial hyperplasia. Using 5-
ALA and extra-vascular light source Nyamekye and his colleagues showed that PDT given during balloon injury in the rat artery completely eliminated the endometrial hyperplasia response at 14 and 28 days.
27 in the same model, complete inhibition of endometrial hyperplasia can be seen after four weeks of treatment with a sensitivity-enhancing agent sulfur-aluminum-benzene salt.
The decrease in positive-treated endometrial hyperplasia continued for 26 weeks compared to the control group.
Similar effects can even be achieved in the transplanted vein.
Vein graft for arterial disease is associated with endometrial hyperplasia in the catheter and in the site of the anastomosis.
In terms of the impact of PDT, there is limited work in this area.
A study carried out in a rat venous transplant model showed that PDT with a sensitivity agent, aluminum chloride, reduced the degree of endometrial hyperplasia in the venous catheter, but did not form a new endometrium in the coincidence
43 pdt application in the coronary and peripheral circulation of pigs has been widely accepted as a suitable model for balloon vascular formation to evaluate new interventional techniques and strategies to combat re-stenosis.
For PDT studies, it has been shown to be particularly useful in assessing compensation techniques that can be used for clinical light delivery.
A thin flexible cylindrical diffuser that can be connected to the end of the optical fiber can be integrated into an in-vessel system for light delivery, illuminating the arterial wall from the inside of the lumen around the circumference.
In earlier studies, these fiber filaments entered the vascular cavity directly, but the blood between the therapeutic field and the light source reduced the efficiency of light delivery, and the bare fibers could not be concentrated in the arterial cavity.
44 another option is to modify the standard vascular forming catheter.
The laser fiber can be placed in the wire guide channel of the transparent balloon catheter and positioned so that the diffuser at the tip of the fiber is located within the balloon segment (fig 3).
21 during balloon inflation, blood is excluded from the arterial cavity, and with balloon inflation, the fibers are concentrated in the arterial cavity, allowing for even illumination of the arterial wall.
In coronary arteries, long balloon inflation has a risk of ischemia, so it may be necessary to deflate repeatedly during lighting to minimize the risk of hypoxia damage.
Download figureOpen modified the standard transparent Asuka vascular forming balloon for in-vessel light delivery in the new tabDownload powerpoint figure 3.
The 100 μm laser fiber with a remote diffuser is placed in the guide wire lumen, making the diffuser located in the balloon segment, allowing for weekly illumination through the entire balloon surface area.
Several groups studied the effects of PDT on the damaged pig arteries.
In a study, gonschio and his colleagues used a porous balloon catheter to locally deliver light-sensitive factors in the femoral artery of pigs damaged with a directional Arterial resection device.
Four groups of animals were investigated.
A control group with injury only, injury only and sensitivity, injury only and laser, and an active treatment group receiving injury and PDT (
Sensor and light).
Light is transmitted by fiber filaments placed directly in the arteries.
The arteries treated with PDT showed a significant decrease in the rate of endometrial hyperplasia within 21 days compared with the control-injured vessels (mean (SD): 0. 3 (0. 2)v 1. 0 (0. 5), pu2009
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