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Effects of MEBO Scar Ointment to Ultra-structure of Hypertrophic Scar
Add Timeú║2011/5/18 13:45:45
Zhang Kai1 Su Pei-mao2 Li Hong-ye3 Liu Tong-lin1 Cui Xiu-zhen4 Lu Zeng-hua4 Liu Wen-bo3
Affiliations: 1. Burn and Plastic Unit of Binzhou Medical University Hospital;
2. Yanggu County Medical School;
3. Electron Microscope Room of Binzhou Medical University Hospital;
4. Pathological Department of Binzhou Medical University Hospital
ú█AbstractúŢ Objective: To explore the mechanism of MEBO Scar Ointment in anti-scarring via the observation of the effects of MEBO Scar Ointment on ultra-structure of hypertrophic scar. Method: Chose 14 patients with hypertrophic scar on both lower extremities recovered from deep II degree burn injuries. Left lower extremities externally administered MEBO Scar Ointment for twice per day in combination with massage therapy were distributed in test group. Right lower extremities were distributed in control group without any interventions except for massage therapy. And performed the electron microscope examinations on scar specimen sectioned from both extremities on the day before the beginning of treatment, at 3rd month, at 6th month and at 12th month during treatment respectively. Results: In test group, the results of electron microscope examination showed decreased fibroblasts, decreased organelles in cytoplasm, apparent reduction of glycogenosome, regular arrangement of collagenous fibers and decreased blood vessels. Conclusion: MEBO Scar Ointment was effectively able to prevent and treat hypertrophic scar.
[Keywords] Hypertrophic scar; ultra-structure; MEBO Scar Ointment      / three monthsn with massage therapyoup without any interventions.  of
Hypertrophic scar is the severe disorder influencing skin functions and morphology. Its pathogenesis is unknown. Currently, its formation and development cannot effectively be controlled. In clinic, the commonly used interventions include surgical removal of scarring, pressure therapy, steroid injections, radiotherapy et alú█1úŢ. Due to the disadvantages of these methods, such as susceptibility to reoccur, long-term therapeutic cycle and occurrence of severe complications, the clinical application is restricted in some extents. It is always the research keys to seek for a simple approach with much less side effects. In clinical practice, we found that MEBO Scar Ointment had good therapeutic effects on hypertrophic scar. This study was designed to provide the theoretical foundation for extensive explanation of its mechanism by means of observing MEBO Scar Ointmentí»s effects on ultra-structure of hypertrophic scar.
1. Study background and methods
1.1 Background: Randomly chose 14 patients with hyertrophic scar on both extremities recovered from deep II degree burn injuries. There were 9 male and 5 female with the age range from 8 to 56. Left lower extremities externally administered MEBO Scar Ointment for twice per day in combination with 15min massage therapy were distributed in test group. Right lower extremities were distributed in control group without any interventions except for massage. And then performed the electron microscope examinations on scar specimen sectioned from both extremities on the day before the beginning of treatment, at 3rd month, at 6th month and at 12th month during treatment respectively.
1.2 Ways to evaluate
Inspection: The color, thickness, quality and surface area of hypertrophic scar in both groups before and after treatment were observed. Light microscope: specimen from both groups were excised and made into histological sections according to traditional methods. And then handled by Haematoxylin, Eosin, VG and compound stains, the sections were observed. Electron microscope: excised 1mm3 specimen containing superficial and sub-superficial scar tissue. And then fixed it with 10% glutaraldehyde. After all specimens were collected, they were conducted the processes of dehydration, embedding and cutting and finally made into 50~70nm slices altogether. And then the uranium dyeing was applied to stain the slices. Finally put prepared specimens under the electron microscope to observe, as well as give the qualitative description and take pictures. The electron microscope is model TEM (transmission electron microscope) X-7500 manufactured by Hitachi Limited with 0.204nm resolutions that can be magnified by 600,000 times.  
2. Results
2.1 Apparent bulging, redness, hardness, itching, extended blood vessels appearing net or branch hypertrophic scarrings were inspected in control group. Scar contracture occurred around joints and affected corresponding functions. In test group, in particular for those given MEBO Scar Ointment for 12 months, the scarring was not significant and the scar became flatness. For those given MEBO Scar Ointment for 3 to 6 months, it could be inspected that the colors of hypertrophic scarring were gradually turned from bright redness to dark with apparent relieve of vascular extension, softness, alleviation of pain and itching symptoms and approximately normal elasticity. Tiny dermatoglyph could be seen on the affected area. The color of dermatoglyph was close to normal surrounding skin. The results showed that the difference of therapeutic effects between two groups was significant.   
2.2 Light microscope: hyperplasic scarring with abundant collagenous fiber was noted in control group. The arrangement of collagenous fiber was messy, appearing mass or turbine-like. There were abundant fibroblasts contained in the mass. The capillaries were extended with the emerging of abnormal mucopolysaccharide. On the sections stained by HE and VG in test group, the structure of collagenous fiber was vague with loose arrangement, shallow staining and apparently decreased cellular components.
2.3 Electron microscope: In control group, fibroblasts at different stages appeared irregular with a few longer cytoplasmic bulging, observable oval nuclei having incisure, distinct euchromatin and heterochromatin condensation. Rough endoplasmic reticulum was dilated. Strong Golgi complex and secretary vesicles could be noted. Collagenous fibers were distributed between cells with different density and disturbed arrangement. The emerging of crossing band appeared node or vortex shape. The gross bundle of collagenous fibers were sectioned between nodes. The collagen with 40 to 80nm diameter had hyaline changes. A few macrophages could be noted, appearing round, oval or irregular; the oval nuclei had indenture with dense chromatin granule. Heterochromatin concentrated beneath nuclear membrane. There contained oval mitochondrion and different numbers of lysosomes and phagocytic particles in cytoplasm. Vascular lumens of micro-vessel were blocked or partially blocked. In test group, the number of fibroblast was decreased. The cord-like fibroblasts had several cytoplasm bulging with swollen and vacuolized mitochondrion. The numbers of organelles in cytoplasm reduced. The decreasing of glycogen particles was apparent. The arrangement of collagenous fiber was regular and fine bouquet with little cellular components. The mitochondrion and endoplastic reticulum of vascular endothelial cells were highly dilated with the emerging of large vacuoles and the phenomenon of nucleus breakdown. The number of vessel decreased. The lumen of vessels was narrowed, even closed.  
3. Discussion
3.1 Pathological characteristics of hypertrophic scar: Hypertrophic scar is the remnant pathological structure after the recovery of injured dermis that is redness and hardness and elevated from surrounding skin. It is the disorder of skin fibrosis with the features of overproduction and deposition of extracellular matrix. The basic unit of structure is collagen node in which contains high-density fibroblast and collagen fibers with the arrangement of single direction and high density. Micro-vessels appeared reticular, encircling main body of node in which contained extremely decreasing number of vessels. Due to the increased level of vascular endoepithelial cells, most of micro-vessels were partially or completely blocked.  
3.2 The course of treatment and changes of scar ultra-structure: It is time dependency for the emerging of scar hypertrophy after got injured. During the early stage of healing, scar is unobvious. With the time passing by, scar tissue will be elevated and become hardness with increasing pruritus. If no interventions were given, the process of scarring will last for a long time. The use of MEBO Scar Ointment might reverse this process. But it is still a long-term process. Therefore, it must adhere to the use of MEBO Scar Ointment, never stop during the course of treatment. As long as the entire course of treatment is followed, often the positive clinical results will be gained. Or the improvement of scarring will be not obvious. The massage therapy following the external use of MEBO Scar Ointment can improve the therapeutic effects. The procedures of massage therapy: Repeatedly press, rotate and rub with the strength of pulp and palm on the affected area topped up with MEBO Scar Ointment. Perform the massage for 15 minutes after the use of MEBO Scar Ointment. Someone reported that better therapeutic effectiveness would be achieved in association with pressure therapy after massageú█2úŢ.
3.3 The probable mechanism of MEBO Scar Ointment: Kischerú█3úŢ using electron microscope found that the increased number of endoepithelial cells in hypertrophic scar led to partial or complete block of most micr-vessels that further resulted in decreased level of PaO2 and elevated level of PaCO2. For the newly proliferated fibroblasts and generated mitosis-promoting factors are seldom to be taken away with blood flow. The lowered level of oxygen stimulates the dilation of capillaries, the protruding of endoepithelial cells and then the differentiation of endoepithelial cells into muscular fibroblasts and fibroblasts. Abundant synthesis of collagen and deposition of fibrous proteins result in vascular block that aggravates hypoxia. Formation of the malignant circle extensively causes scarring. Hereby, the mechanism of MEBO Scar Ointment might be its improvement of regional blood circulation, correction of regional hypoxia, acceleration of tissue repairing and suppression of fibrous proliferation to prevent scarring.
[1] Larson DLúČAbston SúČEvans EBúČet al. Techniques for decreasingscar formation and contractures in the burned patientsú█ú╩úŢú«J TraumaúČ1971ú╗11ú║807
 [2] Li Chuan-yan, Yan Hong-mei, Hu Jian-bin, et al. The clinical application of MEBO Scar Ointment in prevention of hypertrophic scar and scars [J]. The Chinese Journal of Burns Wounds & Surface Ulcers, 2000; (1): 23
[3]Kischer CWúČThies ACúČChvapil MúČet al. Perivascular myofibroblasts  and  microvascular  occlusion  in  hypertrophic  scars  andkeloidsú█ú╩úŢú«Hum SpatholúČ1982ú╗13úĘ9úęú║910
 (Paper received on Oct 15th, 2001)
 (From The Journal of Binzhou Medical University 2002, Vol. 25. No. 1)

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