الفهرس 
IntroductionOnly 14 pages are availabe for public view
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Abstract
Wound healing is a complex group of biochemical and cellular events designed to achieve restoration of tissue integrity. Upon injury of the skin, a set of complex biochemical events takes place to repair the damage. Phases of wound healing include hemostasis , inflammation, proliferation and remodeling. Wound healing may be complicated by excessive scarring, which has unpleasant physical, psychological and social consequences. Scars may be keloids or hypertrophic scars. Keloids are excessive scars that grow beyond the boundaries of the original wound. They do not spontaneously regress and frequently recur after being excised .They are usually resulting from surgery, trauma, burn injuries or extensive soft tissue trauma. Hypertrophic scars stay within the boundaries of the original lesion and may spontaneously regress with time. Hypertrophic scars can be classified as linear or widespread. Leptin is one of adipokines and has an active role in regulating energy homeostasis, metabolism and immune inflammatory processes, in addition to being a hypothalamic modulator of food intake, body weight and fat stores. Leptin has a role in normal wound healing via its ability to induce neovascularization, stimulating effects on macrophages, lymphocytes, keratinocytes, and fibroblasts during tissue repair and regulation of cytokines expression. This study aimed at evaluating the possible role of leptin in abnormal wound healing through its immunohistochemical expression in keloid and hypertrophic scars and to study the relationship of this expression with clinico-pathologic parameters of studied cases. This case-control study was carried out on 80 subjects. These included 20 cases with keloid , 20 cases with hypertrophic scar, 20 cases with granulation tissue and 20 age, gender and body mass index matched normal subjects as a control group. Cases were selected from Dermatology and Plastic Surgery Outpatient Clinics, Menoufiya University Hospital. Cases were either newly diagnosed or old ones with no history of topical or systemic therapy for at least 6 months before the study initiation. Every case was subjected to complete history taking, complete general examination and Dermatologic assessment of the lesion according to Manchester Clinical Assessment Sheet. Non obese subjects were selected based on BMI values {weight (Kg)/height (m2)}.The study included those with BMI between 19-25 Kg /m2. Overweight (BMI: >25-29 Kg/m2) and obese (BMI >30 Kg/m2) subjects were excluded from the study. Patients with type I and type II diabetes mellitus, patients with concomitant disorder(s) that may affect the outcome of the study, subjects taking any drug that affect leptin expression and/or glucose metabolism (insulin, glucocorticoids , estrogens, glucosamine , short chain fatty acids , catecholamines , thyroid hormones, androgen and adrenergic agonists), subjects with metabolic syndrome and with unsteady weight in the past three months were also excluded. Identification of metabolic syndrome was done using updated National Cholesterol Education Program criteria. Punch skin biopsies were taken under local anesthesia. All biopsies were fixed in 10% neutral buffered formalin, dehydrated in ascending grades of ethanol followed by xylene then impregnated in paraffin. Four 5 micron (5μ) thick sections from each block were obtained. One section was stained by Haematoxylin and Eosin (H&E) for histopathological examination. The other sections were mounted on positively charged slides (Fisher Scientific) until used for immunostaining with leptin. All cases of keloid showed positive epidermal expression of leptin (100%), with patchy localization in (40%) of cases and diffuse localization in (60%). Epidermal intensity was moderate in (50%) of cases and strong in (50%). Pattern of leptin staining was cytoplasmic in (60%) of case, nuclear in (20%) and nucleo-cytoplasmic in (20%). Regarding leptin dermal expression, all the studied keloid cases showed positive staining with dermal localization in fibroblasts and blood vessels. Dermal intensity was mild in (20%) of cases and moderate in (80%). Pattern of dermal staining was cytoplasmic in (60%) of cases and nucleocytoplasmic in (40%). Hypertrophic scars showed positive epidermal expression of in (75%) of cases. All positive cases had a patchy localization and nuclear pattern of staining (100%). Epidermal intensity was mild in (53.3%) and moderate in (46.7%) of positive cases. Leptin expression in dermis of hypertrophic scars showed positive staining with dermal localization in myofibroblasts and blood vessels in (70%) of cases. Dermal intensity was mild in (42.9%) and moderate in (57.1%). Pattern of dermal staining was cytoplasmic in (85.7%) and nucleocytoplasmic in (14.3%). All cases of granulation tissue showed positive staining of leptin in myofibroblasts and blood vessels with nucleo-cytoplasmic pattern of staining. Staining intensity was moderate in (60%) and strong in (40%) of cases. Immunohistochemical expression of leptin in epidermis of normal skin showed positive expression with diffuse localization in all examined specimens (100%). Epidermal intensity was mild in (70%) and moderate in (30%) of sections. (70%) showed cytoplasmic pattern of staining and (30%) showed nucleo-cytoplasmic pattern. Dermis of all normal skin samples (100%) showed positive staining of leptin with localization in myofibroblasts and blood vessels. (10%) had nucleo-cytoplasmic pattern of staining and (90%) had cytoplasmic pattern. Dermal intensity was mild in (90%) and moderate in (10%) of samples. Keloid cases showed significantly higher epidermal H score, epidermal intensity, dermal H score and dermal intensity (P<0.001 for all) compared to normal skin. Normal skin showed enhanced leptin immunostaining as diffuse epidermal immunoreactivity was significantly higher compared to keloid cases (P= 0.002). Hypertrophic scar cases showed significantly higher epidermal H score (P<0.001) , dermal H score (P<0.001) and dermal intensity (P<0.01) compared to normal skin. Normal skin showed enhanced leptin immunostaining as epidermal positivity (P=0.02), diffuse epidermal immunoreactivity (P<0.001) and dermal positivity (P=0.03) were significantly higher compared to hypertrophic scar cases. Granulation tissue cases showed significantly higher dermal H score (P<0.001), dermal intensity (P<0.001) and nucleo-cytoplasmic pattern of staining (P<0.001) compared to normal skin. Keloid showed significantly diffuse epidermal localization (P= 0.008), higher epidermal intensity (P=0.01), dermal positivity (P=0.02) and dermal intensity (P=0.002) compared to HS. Nuclear pattern was significantly associated with HS (P<0.001). Leptin H score was significantly associated with female cases, older age group of the studied cases and keloid cases with positive family history, whether familial or hereditary factors play a role in leptin expression or not, needs further investigations. In conclusion, the results obtained in the current study indicate that in-situ leptin overexpression may increase the possibility of keloid and hypertrophic scar occurrence through altered cytokine production and prolonged healing phases with excessive deposition and delayed collagen degradation. This may open an avenue for research for new therapeutic modalities based on leptin inhibition.