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Histopathological timing of wound:
Gross changes:
• A bright red color of a wound is developed 0-4 hours post-injury, may remain for further 12 hours.
• Reddish scab is present 12-24 hours and may extend to 72 hours.
• A brownish scab may be seen 24-72 hours and a maximum of 5 days.
• A dark brown scab may be present 4-6 days.
• A black scab is developed 7-14 days (5-21 days).
• A scab fallen-margin 7-14 days and may be more than 2 weeks old.
• Fallen of a scab compeletly about 17 days post injury.

Microscopic changes:
• Congestion/ hemorrhage about 10 min (0-4 hs )
• Oedema formation 15 min (0-4 hs )
• Margination of polymorph cells 30 min (0-4 hs )
• Early infiltration of neutrophil cells 6 hs (4-12 hs )
• Predominant neutrophilic infiltration 12hs (12-24 hs )
• Mononuclear cell infiltration 24 hs (24-72 hs )
• Fibroblast formation 71 hs (71-78 hs)
• Granulation tissue deposition 72 hs (4-6 days )
• Collagen formation 96 hs (4 days) 7-14 days
• Regression phase 213 hs (9 days) >2 weeks
Role of Cytokines in wound healing:
Cytokines are a family of secretory and regulatory molecules of protein or glycosylated as glycoprotein with a (hormone-like) activity and molecular weight ranging from 10 to 50 KiloDalton 1.
Cytokines are produced transiently and locally-acting in a paracrine or autocrine rather than endocrine manner and they are extremely potent with only tiny amounts required to induce an action and sometimes acting through no more than 10-15 receptors per cell. Cytokines interact with high affinity cell surface receptors specific for each cytokine or cytokines group which when bound leads to altered cell behaviour. Individual cytokines may have multiple overlapping cell regulatory actions 2. They facilitate the communication between cells especially those of the haemopoietic and neuroendocrine systems (Inter-cells messengers).
Cytokines are cellular regulatory proteins released from specialised cells in response to various stimuli and affect the behaviour of target cells. Cytokines include interleukins,chemokines, growth factors, lymphokines, myokines,colony-stimulating factors (CSFs), transforming growth factors (TGFs), tumour necrosis factors (TNFs) and interferons.20 Cytokines are markers that exhibit a surge particularly
in the early stage of wound healing.
Certain conditions affect the timing of release and amount of cytokines, among these, severe malnutrition, malignant diseases and metabolic disorders, medical therapies with glucocorticoids and cytostatic agents and exposure to chronic radiation have several unfavourable effects on wound healing and delay the healing process; differences in cytokine values have been demonstrated at such instances.19,29
Cytokines are polypeptide molecules usually glycosylated produced by a broad range of cells, including activated lymphocytes and macrophages; they are actively involved in the regulation of the functions of other cells.
30, 31
Cytokines can act on the cells that produce them as well as other cells in the close vicinity and have systemic effects. Cytokines have local effects on the endothelium, leukocytes and ?broblasts.31I. Birincio
Cytokines modulate various biological events and play important roles in the immune, central nervous, endocrine and haematopoietic systems. The interleukins (ILs) IL-1(interleukin one) and IL-6 (interleukin six) are pro-in?ammatory cytokines that are constitutively present in keratinocytes and the sweat glands of uninjured skin.
Disruption of the epidermal barrier (wound injury) results in the release of the pre-stored IL-1 and IL-6 from keratinocytes. IL-1 and IL-6 alert the surrounding cells regarding signs of barrier damage.
In addition, tissue injury causes disruption of blood vessels with
Blood constituents extravasation. The resulting clot induces haemostasis and provides a matrix for the in?ux of in?ammatory cells. Platelets also secrete growth factors such as epidermal growth factor (EGF), platelet-derived growth factor (PDGF) and transforming growth factor-beta (TGF-b) and several chemokines. These proteins promote further recruitment of in?ammatory cells to the site of injury,mainly neutrophils.
Macrophages play a crucial role in augmenting the in?ammatory response and tissue debridement. Macrophages also initiate the development of granulation tissue and release various proin?ammatory cytokines (IL-1 and IL-6) and growth factors ?broblast growth factor (FGF), EGFepidermal growth factor, TGF-b(transforming growth factor beta) and PDGF. Within hours of injury, re-epithelialisation is initiated and the release of EGF, TGF-a and FGF acts to stimulate epithelial cell migration and proliferation.

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