MINISTRY OF EDUCATION MINISTRY OF NATIONAL AND TRAINING DEFENCE VIETNAM MILITARY MEDICAL UNIVERSITY NGUYEN THANH CHUNG STUDY ON TOPICAL TREATMENT EFFECT OF CERIUM NITRATE 2.2% GEL ON THERMAL BURN WOUNDS PhD. MEDICAL DISSERTATION HA NOI - 2021 MINISTRY OF EDUCATION MINISTRY OF NATIONAL AND TRAINING DEFENCE VIETNAM MILITARY MEDICAL UNIVERSITY NGUYEN THANH CHUNG STUDY ON TOPICAL TREATMENT EFFECT OF CERIUM NITRATE 2.2% GEL ON THERMAL BURN WOUNDS Specialty: Surgery Code: 9720104 PhD. MEDICAL DISSERTATION SCIENTIFIC INSTRUCTORS: Assoc. NGUYEN NGOC TUAN, MD.
PhD DO LUONG TUAN, MD. PhD HA NOI - 2021 DECLARATION I declare that this is my own work, and the research results presented in the dissertation are truthful, objective, and have never been used in any other studier. I hereby declare that all help in conducting the research has been acknowledged, and the information in this dissertation has been cited. Hanoi, 2021 Author NGUYEN THANH CHUNG ACKNOWLEDGMENTS During the process of studying and completing this dissertation, I have received valuable guidance and help from teachers, scientists, departments, faculties, agencies, and units.
I would like to thank the Party Committee and Board of Directors of Le Huu Trac National Burn Hospital, relevant organization, Post Graduate Department - Vietnam Military Medical University for creating faverable conditions and allowing me to study, research and complete the dissertation. I would like to express my deep gratitude to my two supervisors: Senior Colonel Assoc. Nguyen Ngoc Tuan and Senior Colonel Dr. Do Luong Tuan who wholeheartedly helped me throughout the process of studying, implementing and completing the dissertation.
I would like to thank my family and friends who encouraged and supported me doing the study and completion of my dissertation. Author Nguyen Thanh Chung TABLE OF CONTENTS DECLARATION ACKNOWLEDGMENTS TABLE OF CONTENTS APPENDICES LIST OF ABBREVIATIONS LIST OF TABLES LIST OF DIAGRAMS LIST OF FIGURES INTRODUCTION. CLASSIFICATIONS OF BURN DEPTH. PROCESS OF BURN WOUND HEALING.
The proliferative phase. Maturation phase, scar formation. THE BURN WOUND INFECTION AND TOPICAL DRUGS FOR TREATMENT OF THE BURN WOUND INFECTION. Burn wound infection.
Drugs to treat burn wound infection. CERIUM NITRATE AND APPLICATIONS IN BURN TREATMENT. Cerium and Cerium nitrate overview. Some biological effects of Cerium.
The application of cerium nitrate in burn treatment. Toxicity and adverse effects of Cerium nitrate. Cerium nitrate gel. 35 CHAPTER 2: SUBJECTS AND RESEARCH METHODS.
Subjects of drug toxicity study. Research subjects of antibacterial effect. Research subjects of experimental burn treatment. Research subjects of clinical treatment of burns.
Study methods for acute toxicity of Cerium nitrate. Study method semi-chronic toxicity of Cerium nitrate. Research methods for skin irritation of Cerium nitrate. Evaluation of the antibacterial ability of Cerium nitrate.
Method to evaluate the therapeutic effect of Cerium nitrate gel on experimental burns. Methods of assessing the clinical effectiveness of Cerium nitrate gel. Data processing methods. Limitations and difficulties of the research.
TOXICITY AND ANTIBACTERIAL EFFECTIVENESS OF CERIUM NITRATE. Acute toxicity of Cerium nitrate gel on experimental animals. Semi-chronic toxicity of Cerium nitrate gel on white rats. Study result of skin irritation of Cerium nitrate gel.
The in vitro antibacterial ability on some bacterial species. TOPICAL EFFECTS OF CERIUM NITRATE GEL. Effect of burn wound treatment on experimental mice. Treatment effect on burn wounds in clinical.
ACUTE TOXICITY, SUBACUTE TOXICITY, AND SKIN IRRITATION OF CERIUM NITRATE. Acute toxicity of cerium nitrate gel. Semi-permanent toxicity of the cerium nitrate gel. Skin irritation of cerium nitrate gel.
ASSESSMENT OF THE ANTIMICROBIAL EFFECTS OF CERIUM NITRATE GEL. Causes of burn wound infection. In vitro antibacterial effect of cerium nitrate gel. The minimal inhibitory and complete bactericidal concentration of cerium nitrate gel.
Antibacterial effect of cerium nitrate gel on experimental and clinical burn wounds. TREATMENT EFFECTS OF CERIUM NITRATE GEL ON EXPERIMENTAL AND CLINICAL BURN WOUNDS. Anti-inflammatory and anti-edema effects of cerium nitrate. The drying effect for necrosis of cerium nitrate.
Immunological effects of cerium nitrate gel. Safety of cerium nitrate gel. Initial evaluation of the clinical effect of cerium nitrate gel. 140 LIST OF PUBLISHED ARTICLES RELATED TO THE DISSERTATION REFERENCES APPENDICES LIST OF ABBREVIATIONS No.
Abbreviations Full text 1 Aci. baumannii Acinetobacter baumannii 2 BSA Body surface are 3 ECM Extracellular Matrix 4 E. coli Escherichia coli 5 FGF Fibroblast growth factor 6 EGF Epidermal growth factor 7 ICU Intensive Care Unit 8 K. pneumoniae Klebsiella pneumoniae 9 LPC Lipid protein complex 10 MBC Minimum Bactericidal Concentration 11 MIC Minimum Inhibitor Concentration 12 MMP Matrix Metalloproteinase 13 MPS Mucopolysaccharide 14 OECD Organization for Economic Co-operation and Development 15 P.
aeruginosa Pseudomonas aeruginosa 16 PDGF Platelet derived growth factor 17 S. aureus Staphylococcus aureus 18 S. epidermidis Staphylococcus epidermidis 19 SSD Silver Sulfadiazine 20 SB Standard Basis 21 TGF β Transforming growth foctor-β 22 VEGF Vascular endothelial growth factor LIST OF TABLES Tables Name of Tables Page 2. Evaluation and classification of skin irritation in rabbits.
Death rate of mice after 14 days using orrally Cerium nitrate gel. Some manifestations of rats after drinking cerium nitrate gel. The changes in mice weight when drinking Cerium nitrate gel. Changes of hematological and blood biochemical indicators of mice 68 3.
The irritation of Cerium nitrate gel on healthy rabbit skin. Effect of Cerium nitrate gel on negative gram bacteria. Effect of Cerium nitrate gel on positive gram bacteria. The relationship between the counted bacteria and drug concentrations along contact time.
Weight changes (g) of the mouse during research. Local manifestation of experimental burn wound. Changes in burn size through treatment time. Experimental burn wound healing time.
Percentage of positive bacteria isolated in burn wounds. The percentage of bacterial strains on burn wounds. Density of bacteria on the wound surface with positive cultures. Changes in some hematological indexes of experimental rats.
Changes in some biochemical indicators of mice. Some characteristics of the study group. Progression of deep dermal burn necrosis. Necrosis progression of deep dermal burn wounds.
Percentage of positive cultures on deep dermal burn wounds. The percentage of bacterial species in the deep dermal burn wound. The density of bacteria/cm2 of deep dermal burn wounds. Changes in hematological indices in patients with deep dermal burns.
Changes in blood biochemistry index in patients with deep dermal burns. Cytological changes on the surface of deep dermal burns. Local progression of deep burn wounds. Progression of local necrosis of the deep burn wound.
Percentage of deep burn wounds with positive cultures. The proportion of bacterial species in deep burns. Number of bacteria per 1 cm2 of deep burn wound. Changes in hematological parameters in patients with deep burns treated with Cerium nitrate.
Blood biochemistry indices in patients with deep burns treated with Cerium nitrate. Histopathological changes of deep burn wounds. 104 LIST OF DIAGRAMS Diagram Name of Diagram Page 4. Effect of cerium nitrate.
127 LIST OF FIGURES Figure Name of Figures Page 1. Pathophysiology of wound healing. The wound covered by membrance created by Flammacerium containing calcium. Two ways causing dermal Calcification in wounds treated with Cerium nitrate.
Trial drug and placebo drug. Automated hematology testing machine. Semi-automatic biochemistry analyzer. Creating experimental burn instrument.
Biopsy device (Biopsy Punch) used in research. Olympus CX41 optical microscope with photo shooting system. Research designed diagram. Morphology of liver structure, kidney and spleen of rat after 14 days drinking Cerium nitrate gel.
Rat liver, kidney and spleen structure after 4 weeks of drinking Cerium nitrate gel. Rabbit skin at the times of exposure to Cerium nitrate gel. The chat of sterile ring diameter of drugs with gram negative bacteria. Chart of sterile ring diameter of Cerium nitrate gel with bacteria.
Image of injury after post burns. Image of injury after 7 days of treatment. Image of injury after 14 days of treatment. Image of injury after 21 days of treatment.
Image of injury after the treatment was cured. Fire deep dermal burn injury on the 3rd day after burn. Deep dermal burn injury in the first week of study. Deep dermal burn injury in zone A, 7th day of study.
Deep dermal burn injury on 16th day. Deep dermal burn injury on 18th day. Applying the drug to treat deep burns on the right leg on the first day of the study. Characteristics of deep burn injury on the 6th day of study.
Necrotomy and skin grafting for deep burn lesions. Results of skin grafting for deep burns. Nuclear medicine images of mice on the 3rd and 7th day after the burn. aeruginosa at the time of exposure to cerium nitrate gel PL2.
Morphology of tissue structure of deep burns in area A before drug application PL3. Morphology of tissue structure of deep burns in area A on the 3 rd day of application PL4. Morphology of tissue structure of deep burns in area A on the 7 th day of application PL5. Morphology of tissue structure of deep burns in area B before drug application PL6.
Morphology of tissue structure of deep burns in area B on the 3rd day of application PL7. Structural morphology of deep burns in area B on the 7th day of application 1 INTRODUCTION Burn is an acute injury to the body caused by heat, chemicals, electricity, and radiation. Burn injuries disrupt body functions and systemic responses to protect and heal. The process from the time of burn, may arise systemic dysfunction and changes at the burn site manifested by pathological syndromes appearing with regularity called “burn disease” [1].
Burns are the leading cause of injury, with more than 300,000 deaths globally each year. The rate of burns in developing countries is significantly higher than in developed countries. The average number of victims per year in Russia is 170.000, and in the UK it is 140,000 [2], [3]. Burn infection is a common complication, adversely affecting the healing process, prolonging the treatment time, if the infection is severe, it also affects the whole body.
Wet necrotic burns are severe due to the necrosis and absorption into the body, causing a state of toxicity, wet necrosis is also a nutritional environment for bacteria to grow, causing local and systemic infections, and slowing down the healing process, and are prone to secondary necrosis [4], [5]. Despite advances in resuscitation, nutrition, and surgery, mortality in severe burns remains high, especially in developing countries. The main cause is an infection, and multi-organ failure, which are mainly causes from burn injuries. The basic principle of treatment for extensive burns is surgical, intervention and to cover with autologous skin.
However, due to the lack of autologous skin and temporary skin substitutes as well as difficulties in resuscitation during and after surgery in patients with extensive burns, inhalation injury, the treatment of extensive burns is still difficult. The reasonable solution is partial surgery, each stage along with minimizing the bad progress in the remaining deep burns [3]. 2 Cerium nitrate is an effective antibacterial product for local treatment of burn wounds, be cause it neutralizes the effect of burn toxins, dries up wet necrosis, and contributing to reduce burn mortality [6], [7]. Experimental research by Eski M.
According to Jakupec M. (2005), cerium nitrate in combination with silver sulfadiazine has been used for local treatment of extensive burns that cannot be removed early. Beside direct antiseptic effect, cerium also helped to prevent post-burn sepsis and systemic inflammatory response by immobilizing burn toxins [7]. Cerium nitrate also had other advantages of high safety and poor absorption into the body.