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Tendon Injuries - Healing Mechanisms and Interventions.

Record Type:	Electronic resources : Monograph/item
Title/Author:	Tendon Injuries - Healing Mechanisms and Interventions./
Author:	Hung, Leung Kim.
Published:	Ann Arbor : ProQuest Dissertations & Theses, : 2016,
Description:	230 p.
Notes:	Source: Dissertations Abstracts International, Volume: 78-06, Section: B.
Contained By:	Dissertations Abstracts International78-06B.
Subject:	Molecular biology. -
Online resource:	http://pqdd.sinica.edu.tw/twdaoapp/servlet/advanced?query=10300432
ISBN:	9781369426045

Tendon Injuries - Healing Mechanisms and Interventions.
Hung, Leung Kim.

Tendon Injuries - Healing Mechanisms and Interventions. - Ann Arbor : ProQuest Dissertations & Theses, 2016 - 230 p.

Source: Dissertations Abstracts International, Volume: 78-06, Section: B.

Thesis (M.D.)--The Chinese University of Hong Kong (Hong Kong), 2016.

This item is not available from ProQuest Dissertations & Theses.

This dissertation investigated two mechanisms that may influence tendon healing, namely mechanical stimulation and oxidative stress, and the potential benefits of local application of vitamin C or E as antioxidants. Background information about different aspects of tendon healing and interventions was reviewed in Chapter 1, and techniques for investigation and treatment of tendon injuries, particular those used in the experiments in the thesis, were reviewed in Chapter 2. Chapter 3: The effects of mechanical stimulation on the tissue level were studied using low-intensity pulsed ultrasound (LIPUS), with a patellar tendon injury model. Gene responses were measured by the mRNA at 4 and 24 hours after a brief 20 minutes treatment of LIPUS. There was an early up-regulation of COL1A1 and TGF-beta1 mRNA in the proliferative-granulation phase of tendon healing, and a late down-regulation of decorin and biglycan mRNA in the remodeling phase. The results could explain the therapeutic window effect of LIPUS observed in a previous study, and the clinical effectiveness of ultrasound to resolve fibrosis and scars. Chapter 4: The effects of imposed oxidative stress on the healing tendon was studied by injecting hydrogen peroxide around a healing patellar tendon wound from 2 weeks to 4 weeks after surgery, given weekly. There was impaired gait pattern and a weakened tendon with persistence of hypercellularity and hypervascularity assessed at 6 weeks. Chapter 5: The effects of hydrogen peroxide and vitamin C on cultures of tendon cells were studied. The progenitor cell-like cloning of tendon cells was impaired by hydrogen peroxide, which also impaired cell proliferation. Vitamin C at low dose promoted the cloning of progenitor-like cells, and was a chemoattractant to tendon cells and enhanced proliferation. High dose vitamin C showed a suppressive effect. Chapter 6: The effects of locally applied vitamin C were studied in the patellar tendon injury model. Vitamin C solution was irrigated to the tendon wound immediately after surgery. The animals were allowed free roaming and final assessment was done at 6 weeks. Assessments at different time points included gait pattern (Limb Idleness Index), high resolution ultrasound imaging, histology, immunohistology for isoforms of nitric oxide synthase, tenomodulin and neutrophil elastase, and mechanical testing of the patellar tendon. The results showed that in the low dose vitamin C irrigation group there was an improved walking pattern, and mechanical strength of the tendon. There was also an enhanced appearance of NOS isoforms which suggested a possible interaction between vitamin C, oxidative stress and NOS actions. There were negative results with high dose vitamin C irrigation, which raised the concern of a pro-oxidant effect of high dose vitamin C. Chapter 7: The effects of locally applied vitamin C and E were studied in the chicken paw flexor tendon injury model. The part of the deep flexor tendon located inside the flexor sheath at the base of the digit was operated. After closure of the flexor sheath either vitamin C solution or Trolox solution, a vitamin E analogue, was injected into the sheath. The paw was immobilized for 2 weeks without any proximal tenotomy, and final assessment was performed at 6 weeks. Assessments at different time points included high resolution ultrasound imaging of the healing tendon, video-assisted tendon gliding test, tissue glutathione ratio (GSH/GSSG) and histology. The results showed that there was decrease in GSH/GSSG ratio after tendon injury. GSH was increased after vitamin C treatment. Low dose of vitamin C and both dosage of Trolox improved the digit flexion and reduced gliding resistance at different time points. There was no benefit with high dose of vitamin C. The results raised the concern of a pro-oxidant effect with high dose of vitamin C. In summary, the studies demonstrated the impact of LIPUS on up-regulation of certain genes responsible for tendon healing. The impact of oxidative stress in tendon injury was demonstrated, which possibly caused damage to the tendon cells, favoring a fibroblastic development. Locally applied vitamin C at a low dose, and vitamin E improved tendon healing, possibly acting through their anti-oxidant actions at the time of injury. It was likely that a local, "one-touch" treatment with vitamin C or E, at an appropriate dosage, could be developed for clinical use. The possible interaction between vitamin C and NOS isoforms is worth investigating further. The specific role of different tendon cells also requires further studies8, in particular the progenitor cell population within a tendon, including their location, and their behavior under different stimulations that may favour a tenogenic healing of the injured tendon.

ISBN: 9781369426045Subjects--Topical Terms:

517296
Molecular biology.
Subjects--Index Terms:

Hydrogen peroxide

Tendon Injuries - Healing Mechanisms and Interventions.
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245 1 0 $a Tendon Injuries - Healing Mechanisms and Interventions.
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300 $a 230 p.
500 $a Source: Dissertations Abstracts International, Volume: 78-06, Section: B.
500 $a Publisher info.: Dissertation/Thesis.
502 $a Thesis (M.D.)--The Chinese University of Hong Kong (Hong Kong), 2016.
506 $a This item is not available from ProQuest Dissertations & Theses.
506 $a This item must not be added to any third party search indexes.
506 $a This item must not be sold to any third party vendors.
520 $a This dissertation investigated two mechanisms that may influence tendon healing, namely mechanical stimulation and oxidative stress, and the potential benefits of local application of vitamin C or E as antioxidants. Background information about different aspects of tendon healing and interventions was reviewed in Chapter 1, and techniques for investigation and treatment of tendon injuries, particular those used in the experiments in the thesis, were reviewed in Chapter 2. Chapter 3: The effects of mechanical stimulation on the tissue level were studied using low-intensity pulsed ultrasound (LIPUS), with a patellar tendon injury model. Gene responses were measured by the mRNA at 4 and 24 hours after a brief 20 minutes treatment of LIPUS. There was an early up-regulation of COL1A1 and TGF-beta1 mRNA in the proliferative-granulation phase of tendon healing, and a late down-regulation of decorin and biglycan mRNA in the remodeling phase. The results could explain the therapeutic window effect of LIPUS observed in a previous study, and the clinical effectiveness of ultrasound to resolve fibrosis and scars. Chapter 4: The effects of imposed oxidative stress on the healing tendon was studied by injecting hydrogen peroxide around a healing patellar tendon wound from 2 weeks to 4 weeks after surgery, given weekly. There was impaired gait pattern and a weakened tendon with persistence of hypercellularity and hypervascularity assessed at 6 weeks. Chapter 5: The effects of hydrogen peroxide and vitamin C on cultures of tendon cells were studied. The progenitor cell-like cloning of tendon cells was impaired by hydrogen peroxide, which also impaired cell proliferation. Vitamin C at low dose promoted the cloning of progenitor-like cells, and was a chemoattractant to tendon cells and enhanced proliferation. High dose vitamin C showed a suppressive effect. Chapter 6: The effects of locally applied vitamin C were studied in the patellar tendon injury model. Vitamin C solution was irrigated to the tendon wound immediately after surgery. The animals were allowed free roaming and final assessment was done at 6 weeks. Assessments at different time points included gait pattern (Limb Idleness Index), high resolution ultrasound imaging, histology, immunohistology for isoforms of nitric oxide synthase, tenomodulin and neutrophil elastase, and mechanical testing of the patellar tendon. The results showed that in the low dose vitamin C irrigation group there was an improved walking pattern, and mechanical strength of the tendon. There was also an enhanced appearance of NOS isoforms which suggested a possible interaction between vitamin C, oxidative stress and NOS actions. There were negative results with high dose vitamin C irrigation, which raised the concern of a pro-oxidant effect of high dose vitamin C. Chapter 7: The effects of locally applied vitamin C and E were studied in the chicken paw flexor tendon injury model. The part of the deep flexor tendon located inside the flexor sheath at the base of the digit was operated. After closure of the flexor sheath either vitamin C solution or Trolox solution, a vitamin E analogue, was injected into the sheath. The paw was immobilized for 2 weeks without any proximal tenotomy, and final assessment was performed at 6 weeks. Assessments at different time points included high resolution ultrasound imaging of the healing tendon, video-assisted tendon gliding test, tissue glutathione ratio (GSH/GSSG) and histology. The results showed that there was decrease in GSH/GSSG ratio after tendon injury. GSH was increased after vitamin C treatment. Low dose of vitamin C and both dosage of Trolox improved the digit flexion and reduced gliding resistance at different time points. There was no benefit with high dose of vitamin C. The results raised the concern of a pro-oxidant effect with high dose of vitamin C. In summary, the studies demonstrated the impact of LIPUS on up-regulation of certain genes responsible for tendon healing. The impact of oxidative stress in tendon injury was demonstrated, which possibly caused damage to the tendon cells, favoring a fibroblastic development. Locally applied vitamin C at a low dose, and vitamin E improved tendon healing, possibly acting through their anti-oxidant actions at the time of injury. It was likely that a local, "one-touch" treatment with vitamin C or E, at an appropriate dosage, could be developed for clinical use. The possible interaction between vitamin C and NOS isoforms is worth investigating further. The specific role of different tendon cells also requires further studies8, in particular the progenitor cell population within a tendon, including their location, and their behavior under different stimulations that may favour a tenogenic healing of the injured tendon.
590 $a School code: 1307.
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650 4 $a Cellular biology. $3 3172791
650 4 $a Surgery. $3 707153
653 $a Hydrogen peroxide
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653 $a Oxidative stress
653 $a Tendon progenitor cells
653 $a Ultrasound therapy
653 $a Vitamin C
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710 2 $a The Chinese University of Hong Kong (Hong Kong). $3 1017547
773 0 $t Dissertations Abstracts International $g 78-06B.
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793 $a English
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